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Shukla S, Khanna S, Khanna K. Unveiling the toxicity of micro-nanoplastics: A systematic exploration of understanding environmental and health implications. Toxicol Rep 2025; 14:101844. [PMID: 39811819 PMCID: PMC11730953 DOI: 10.1016/j.toxrep.2024.101844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 11/21/2024] [Accepted: 11/28/2024] [Indexed: 01/16/2025] Open
Abstract
The surge in plastic production has spurred a global crisis as plastic pollution intensifies, with microplastics and nanoplastics emerging as notable environmental threats. Due to their miniature size, these particles are ubiquitous across ecosystems and pose severe hazards as they are ingested and bioaccumulate within organisms. Although global plastic production has reached an alarming 400.3 MTs, recycling efforts remain limited, with only 18.5 MTs being recycled. Currently, out of the total plastic waste, 49.6 % is converted into energy, 27 % is recycled, and 23.5 % is recovered as material, indicating a need for better waste management practices to combat the escalating pollution levels. Research studies on micro-nanoplastics have primarily concentrated on their environmental presence and laboratory-based toxicity studies. This review critically examines the sources and detection methods for micro-nanoplastics, emphasising their toxicological effects and ecological impacts. Organisms like zebrafish and rats serve as key models for studying these particle's bioaccumulative potential, showcasing adverse effects that extend to DNA damage, oxidative stress, and cellular apoptosis. Studies reveal that micro-nanoplastics can permeate biological barriers, including the blood-brain barrier, neurological imbalance, cardiac, respiratory, and dermatological disorders. These health risks, particularly relevant for humans, underscore the urgency for broader, real-world studies beyond controlled laboratory conditions. Additionally, the review discusses innovative energy-harvesting technologies as sustainable alternatives for plastic waste utilisation, particularly valuable for energy-deficient regions. These strategies aim to simultaneously address energy demands and mitigate plastic waste. This approach aligns with global sustainability goals, providing a promising avenue for both pollution reduction and energy generation. The review calls for further research to enhance detection techniques, assess long-term environmental impacts, and explore sustainable solutions that integrate energy recovery with pollution mitigation, especially in regions most affected by both energy shortages and increased plastic waste.
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Affiliation(s)
- Saurabh Shukla
- School of Forensic Sciences, Centurion University of Technology and Management, Bhubaneswar Campus, Bhubaneswar, Odisha 752050, India
| | - Sakshum Khanna
- School of Technology, Pandit Deendayal Energy University, Gandhinagar, Gujarat 382007, India
- Relx Pvt Ltd, Gurugram, Haryana 122002, India
| | - Kushagra Khanna
- Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia
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Das SK, Sen K, Ghosh B, Ghosh N, Sinha K, Sil PC. Molecular mechanism of nanomaterials induced liver injury: A review. World J Hepatol 2024; 16:566-600. [PMID: 38689743 PMCID: PMC11056894 DOI: 10.4254/wjh.v16.i4.566] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 02/05/2024] [Accepted: 03/19/2024] [Indexed: 04/24/2024] Open
Abstract
The unique physicochemical properties inherent to nanoscale materials have unveiled numerous potential applications, spanning beyond the pharmaceutical and medical sectors into various consumer industries like food and cosmetics. Consequently, humans encounter nanomaterials through diverse exposure routes, giving rise to potential health considerations. Noteworthy among these materials are silica and specific metallic nanoparticles, extensively utilized in consumer products, which have garnered substantial attention due to their propensity to accumulate and induce adverse effects in the liver. This review paper aims to provide an exhaustive examination of the molecular mechanisms underpinning nanomaterial-induced hepatotoxicity, drawing insights from both in vitro and in vivo studies. Primarily, the most frequently observed manifestations of toxicity following the exposure of cells or animal models to various nanomaterials involve the initiation of oxidative stress and inflammation. Additionally, we delve into the existing in vitro models employed for evaluating the hepatotoxic effects of nanomaterials, emphasizing the persistent endeavors to advance and bolster the reliability of these models for nanotoxicology research.
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Affiliation(s)
- Sanjib Kumar Das
- Department of Zoology, Jhargram Raj College, Jhargram 721507, India
| | - Koushik Sen
- Department of Zoology, Jhargram Raj College, Jhargram 721507, India
| | - Biswatosh Ghosh
- Department of Zoology, Bidhannagar College, Kolkata 700064, India
| | - Nabanita Ghosh
- Department of Zoology, Maulana Azad College, Kolkata 700013, India
| | - Krishnendu Sinha
- Department of Zoology, Jhargram Raj College, Jhargram 721507, India.
| | - Parames C Sil
- Department of Molecular Medicine, Bose Institute, Calcutta 700054, India
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Otake H, Masuda S, Kadowaki R, Ogata F, Nakazawa Y, Yamamoto N, Kawasaki N, Nagai N. Therapeutic Effects of Rebamipide Nanocrystals as Carbopol Gel Formulation Containing Gum Arabic in a Hamster Model of Oral Mucositis. J Oleo Sci 2024; 73:1479-1491. [PMID: 39617430 DOI: 10.5650/jos.ess24160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2025] Open
Abstract
Severe oral mucositis is a major cause of a low quality of life in patients; however, the therapeutic effect of traditional treatments is insufficient. Therefore, we designed a carbopol gel based on rebamipide nanocrystals (REB NCs) and gum arabic (GA-REB@NP), and investigated its efficacy in accelerating wound healing in a hamster model of oral mucositis. REB NCs were prepared by bead milling, and GA- REB@NP were prepared by incorporating REB NCs into a carbopol gel. The REB sizes were measured using a SALD-7100 and NanoSight LM10, and both powder X-ray diffraction and differential thermal analysis were used to analyze the crystalline form. Drug release from the gel formulations and therapeutic effects were evaluated using hamsters. The particles of milled-REB without GA were microsized, whereas the particle size of milled-REB with GA was in the range of 30-180 nm, and the crystalline form was similar to that of REB with or without bead milling. Next, we evaluated the characteristics of GA-REB@NP. The particle size of REB in GA-REB@NP was in the range of 45-200 nm, and drug release from GA-REB@NP was higher than that from the gel incorporating REB microcrystals (GA-REB@MP). In addition, REB nanoparticles were released from GA-REB@NP. Moreover, inhibitors of both clathrin- (dynasore) and caveolae-dependent endocytosis (nystatin) attenuated the enhanced REB levels in the cheek pouches of hamsters treated with GA-REB@NP. GA-REB@NP also enhanced the healing of the wound area compared with GA-REB@MP in hamsters injected with acetic acid. We prepared GA-REB@NP, which provided high REB delivery into the cheek pouch tissue via endocytosis. Additionally, we demonstrated that wound healing in acetic acid-injected hamsters was promoted by the application of GA-REB@NP.
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Affiliation(s)
| | | | | | | | | | - Naoki Yamamoto
- Support Office for Bioresource Research, Research Promotion Headquarters, Fujita Health University
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Kadowaki R, Ogata F, Nishida M, Komatsu M, Otake H, Nakazawa Y, Yamamoto N, Kawasaki N, Nagai N. Therapeutic Effects of Hydrogel Formulations Incorporating Troxipide Nanoparticles on Oral Mucositis in Hamsters. Drug Des Devel Ther 2023; 17:3349-3361. [PMID: 38024531 PMCID: PMC10657765 DOI: 10.2147/dddt.s433776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 11/07/2023] [Indexed: 12/01/2023] Open
Abstract
Purpose Medical therapies, such as the use of anti-inflammatory agents, are commonly used for the treatment of oral mucositis (OM). However, these treatments have limited efficacy in treating severe cases of OM. In this study, we aimed to develop a carbopol gel incorporating troxipide (TRO) nanoparticles and methylcellulose (TRO-NP gel) and demonstrate its efficacy in accelerating wound healing in a hamster model of OM (OM model) induced by acetic acid injection. Methods TRO nanoparticles were prepared using bead milling. The crystalline form was determined by powder X-ray diffraction, and the particle size was measured using a NanoSight LM10 instrument. The drug release was determined using a Franz diffusion cell, and the hamsters injected with acetic acid were selected to evaluate the therapeutic effect of OM. Results After preparing TRO nanoparticles, we observed a mixture of crystals and amorphous TRO, and the particle size of TRO in the TRO-NP gel ranged from 50 to 280 nm. The TRO-NP gel exhibited a more uniform TRO distribution and viscosity compared to the Carbopol gel containing TRO microparticles (TRO-MP gel). However, the solubility of TRO was comparable in both TRO-MP and TRO-NP gels. The TRO-NP gel released a higher amount of TRO than that from the TRO-MP gel, with detectable release of TRO nanoparticles. TRO levels in the cheek pouches of hamsters treated with TRO-NP gel were higher than those treated with TRO-MP gel. The increased TRO levels in the cheek pouches of hamsters treated with TRO-NP gel were attenuated by treatment with 40 μM dynasore, an inhibitor of clathrin-dependent endocytosis (CME). Moreover, the therapeutic effect of the TRO-NP gel was superior to that of the TRO-MP gel in the hamster model of OM. Conclusion We have designed a TRO-NP gel, and this gel showed excellent TRO delivery into the cheek pouch tissue through the CME pathway. Moreover, the TRO-NP gel treatment enhanced wound healing after acetic acid injection.
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Affiliation(s)
- Reita Kadowaki
- Faculty of Pharmacy, Kindai University, Higashi-Osaka, Osaka, Japan
| | - Fumihiko Ogata
- Faculty of Pharmacy, Kindai University, Higashi-Osaka, Osaka, Japan
| | - Miku Nishida
- Faculty of Pharmacy, Kindai University, Higashi-Osaka, Osaka, Japan
| | - Miri Komatsu
- Faculty of Pharmacy, Kindai University, Higashi-Osaka, Osaka, Japan
| | - Hiroko Otake
- Faculty of Pharmacy, Kindai University, Higashi-Osaka, Osaka, Japan
| | - Yosuke Nakazawa
- Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, Japan
| | - Naoki Yamamoto
- Support Office for Bioresource Research, Research Promotion Headquarters, Fujita Health University, Toyoake, Aichi, Japan
| | - Naohito Kawasaki
- Faculty of Pharmacy, Kindai University, Higashi-Osaka, Osaka, Japan
| | - Noriaki Nagai
- Faculty of Pharmacy, Kindai University, Higashi-Osaka, Osaka, Japan
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Makhdoumi P, Hossini H, Pirsaheb M. A review of microplastic pollution in commercial fish for human consumption. REVIEWS ON ENVIRONMENTAL HEALTH 2023; 38:97-109. [PMID: 34973052 DOI: 10.1515/reveh-2021-0103] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 11/17/2021] [Indexed: 06/14/2023]
Abstract
Today microplastics (MPs) have received worldwide attention as an emerging environmental pollution which is one of the four major global environmental threat and health hazard to human as well. Unfortunately, MPs have been founded in the all environments and media include air, water resources, sediments, and soil. It should not be forgotten MPs have also been detected in food and processing products like tuna. MPs can be ingested by marine organisms such as zooplankton, fish and birds. Accumulation and distribution of MPs by commercially important aquatic organisms is expected to lead to greater exposure risk for human populations with possible adverse effects over time. The aim of this work was to review the published literature regarding the contamination of commercial fish muscle for human consumption. Furthermore, a short revision of the environmental contamination and human health effects by MPs are included. We also estimated human daily intake considering the worldwide contamination of commercial fish muscle ranged from 0.016 items/g muscle of fish to 6.06 items/g muscle of fish. MPs have been found in 56.5% of the commercial fish samples analysed here. As fish is used in human food table across the word, they constitute a long-term exposure route for all humans and raise the concern about the potential public health risk.
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Affiliation(s)
- Pouran Makhdoumi
- Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Hooshyar Hossini
- Department of Environmental Health Engineering, Faculty of Health, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Meghdad Pirsaheb
- Department of Environmental Health Engineering, Faculty of Health, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Progress in oral insulin delivery by PLGA nanoparticles for the management of diabetes. Drug Discov Today 2023; 28:103393. [PMID: 36208724 DOI: 10.1016/j.drudis.2022.103393] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 08/28/2022] [Accepted: 09/29/2022] [Indexed: 11/05/2022]
Abstract
Currently, the only practical way to treat type 1 and advanced insulin-dependent type 2 diabetes mellitus (T1/2DM) is the frequent subcutaneous injection of insulin, which is significantly different physiologically from endogenous insulin secretion from pancreatic islets and can lead to hyperinsulinemia, pain, and infection in patients with poor compliance. Hence, oral insulin delivery has been actively pursued to revolutionize the treatment of insulin-dependent diabetes. In this review, we provide an overview of recent progress in developing poly(lactic co-glycolic acid) (PLGA) nanoparticles (NPs) for oral insulin delivery. Different strategies for insulin-loaded PLGA NPs to achieve normoglycemic effects are discussed. Finally, challenges and future perspectives of PLGA NPs for oral insulin delivery are put forward.
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Pang H, Huang X, Xu ZP, Chen C, Han FY. Progress in oral insulin delivery by PLGA nanoparticles for the management of diabetes. Drug Discov Today 2023; 28:103393. [DOI: https:/doi.org/10.1016/j.drudis.2022.103393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/14/2024]
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Sánchez A, Rodríguez-Viso P, Domene A, Orozco H, Vélez D, Devesa V. Dietary microplastics: Occurrence, exposure and health implications. ENVIRONMENTAL RESEARCH 2022; 212:113150. [PMID: 35341751 DOI: 10.1016/j.envres.2022.113150] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 03/01/2022] [Accepted: 03/17/2022] [Indexed: 06/14/2023]
Abstract
The increasing use of plastic materials generates an enormous amount of waste. In the aquatic environment, a significant part of this waste is present in the form of microplastics (MPs)- particles with a diameter of between 0.1 μm and 5 mm. The arrival of these small plastics in the food chain has been recently documented. MPs have been reported in fishery products, drinking water and sea salt among other foods. Their intestinal absorption is considered limited due to their size, however, they contain a mixture of chemicals intentionally added during their manufacture, which could cross the intestinal barrier. Currently there are not enough data to allow an accurate assessment of the risk associated with dietary exposure to MPs. The lack of robust methodologies is undoubtedly one of the main problems. There is limited information on occurrence in dietary sources (drinking water and food), human intake, toxicokinetics and long term toxicity of these contaminants. The present review describes the studies published so far and points to the need for improved knowledge in order to have a more accurate view of the problems posed by MPs.
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Affiliation(s)
- Alicia Sánchez
- Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Calle Agustín Escardino 7, 46980, Paterna, Valencia, Spain
| | - Pilar Rodríguez-Viso
- Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Calle Agustín Escardino 7, 46980, Paterna, Valencia, Spain
| | - Adrián Domene
- Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Calle Agustín Escardino 7, 46980, Paterna, Valencia, Spain
| | - Helena Orozco
- Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Calle Agustín Escardino 7, 46980, Paterna, Valencia, Spain
| | - Dinoraz Vélez
- Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Calle Agustín Escardino 7, 46980, Paterna, Valencia, Spain
| | - Vicenta Devesa
- Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Calle Agustín Escardino 7, 46980, Paterna, Valencia, Spain.
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Wang W, Huang Z, Huang Y, Zhang X, Huang J, Cui Y, Yue X, Ma C, Fu F, Wang W, Wu C, Pan X. Pulmonary delivery nanomedicines towards circumventing physiological barriers: Strategies and characterization approaches. Adv Drug Deliv Rev 2022; 185:114309. [PMID: 35469997 DOI: 10.1016/j.addr.2022.114309] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/28/2022] [Accepted: 04/19/2022] [Indexed: 11/01/2022]
Abstract
Pulmonary delivery of nanomedicines is very promising in lung local disease treatments whereas several physiological barriers limit its application via the interaction with inhaled nanomedicines, namely bio-nano interactions. These bio-nano interactions may affect the pulmonary fate of nanomedicines and impede the distribution of nanomedicines in its targeted region, and subsequently undermine the therapeutic efficacy. Pulmonary diseases are under worse scenarios as the altered physiological barriers generally induce stronger bio-nano interactions. To mitigate the bio-nano interactions and regulate the pulmonary fate of nanomedicines, a number of manipulating strategies were established based on size control, surface modification, charge tuning and co-delivery of mucolytic agents. Visualized and non-visualized characterizations can be employed to validate the robustness of the proposed strategies. This review provides a guiding overview of the physiological barriers affecting the in vivo fate of inhaled nanomedicines, the manipulating strategies, and the validation methods, which will assist with the rational design and application of pulmonary nanomedicine.
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Affiliation(s)
- Wenhao Wang
- School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, Guangdong, PR China.
| | - Zhengwei Huang
- College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong, PR China.
| | - Ying Huang
- College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong, PR China.
| | - Xuejuan Zhang
- College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong, PR China.
| | - Jiayuan Huang
- School of Medicine, Sun Yat-Sen University, Shenzhen 518107, Guangdong, PR China.
| | - Yingtong Cui
- School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, Guangdong, PR China.
| | - Xiao Yue
- School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, Guangdong, PR China.
| | - Cheng Ma
- School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, Guangdong, PR China.
| | - Fangqin Fu
- College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong, PR China.
| | - Wenhua Wang
- School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, Guangdong, PR China.
| | - Chuanbin Wu
- College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong, PR China.
| | - Xin Pan
- School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, Guangdong, PR China.
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de Oliveira GR, de Andrade C, Sotomaior CS, Costa LB. Advances in nanotechnology and the benefits of using cellulose nanofibers in animal nutrition. Vet World 2022; 14:2843-2850. [PMID: 35017829 PMCID: PMC8743779 DOI: 10.14202/vetworld.2021.2843-2850] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 09/22/2021] [Indexed: 11/16/2022] Open
Abstract
The production of cellulose nanofibers promotes the utilization of plant residues that are generated in agro-industries during food processing. The utilization of these plant by-products reduces environmental contamination. Cellulose nanofibers are used in several sectors, including the drug, food, and animal nutrition industries. Many sources of nanofibers used in animal diets can be used as potential fiber substitutes after being processed to improve efficiency. For instance, including nanometric particles of plant fibers (<100 nm) in animal feed may provide excellent physical properties such as high reactivity, a large surface area, and improved nutrient absorption from the diet. Nanotechnology improves the characteristics of fibers that are important for gastrointestinal transit and their utilization as energy sources and substrates for microbial fermentation in the digestive tract of animals. Nanofibers can improve the synthesis of volatile fatty acids and the blood lipid profile, with positive effects on the intestinal health of animals. Moreover, in vitro and in vivo studies have demonstrated promising effects in reducing blood glucose levels without toxic effects on the body. Supplying nanofibers in the diet improve animal performance, increase productivity, and work toward a more sustainable economic development of agribusinesses. The quality of animal products such as meat, milk, and eggs is also reported to be improved with the inclusion of nanominerals in the feed. Overall, the application of nanotechnology to harness the by-products of agro-industries can increase economic viability and sustainability in animal production systems. Therefore, this review presents a current survey on the main research and advances in the utilization of nanotechnology, focusing on cellulose nanofibers in animal feed to improve animal performance.
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Affiliation(s)
- Geovane Rosa de Oliveira
- Graduate Program in Animal Science, School of Medicine and Life Sciences, Pontifícia Universidade Católica do Paraná, PUCPR, Curitiba - PR, Brazil
| | - Carla de Andrade
- Graduate Program in Animal Science, School of Medicine and Life Sciences, Pontifícia Universidade Católica do Paraná, PUCPR, Curitiba - PR, Brazil
| | - Cristina Santos Sotomaior
- Graduate Program in Animal Science, School of Medicine and Life Sciences, Pontifícia Universidade Católica do Paraná, PUCPR, Curitiba - PR, Brazil
| | - Leandro Batista Costa
- Graduate Program in Animal Science, School of Medicine and Life Sciences, Pontifícia Universidade Católica do Paraná, PUCPR, Curitiba - PR, Brazil
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Di Cristo L, Oomen AG, Dekkers S, Moore C, Rocchia W, Murphy F, Johnston HJ, Janer G, Haase A, Stone V, Sabella S. Grouping Hypotheses and an Integrated Approach to Testing and Assessment of Nanomaterials Following Oral Ingestion. NANOMATERIALS (BASEL, SWITZERLAND) 2021; 11:2623. [PMID: 34685072 PMCID: PMC8541163 DOI: 10.3390/nano11102623] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 09/29/2021] [Accepted: 10/01/2021] [Indexed: 02/07/2023]
Abstract
The risk assessment of ingested nanomaterials (NMs) is an important issue. Here we present nine integrated approaches to testing and assessment (IATAs) to group ingested NMs following predefined hypotheses. The IATAs are structured as decision trees and tiered testing strategies for each decision node to support a grouping decision. Implications (e.g., regulatory or precautionary) per group are indicated. IATAs integrate information on durability and biopersistence (dissolution kinetics) to specific hazard endpoints, e.g., inflammation and genotoxicity, which are possibly indicative of toxicity. Based on IATAs, groups of similar nanoforms (NFs) of a NM can be formed, such as very slow dissolving, highly biopersistent and systemically toxic NFs. Reference NMs (ZnO, SiO2 and TiO2) along with related NFs are applied as case studies to testing the oral IATAs. Results based on the Tier 1 level suggest a hierarchy of biodurability and biopersistence of TiO2 > SiO2 > ZnO, and are confirmed by in vivo data (Tier 3 level). Interestingly, our analysis suggests that TiO2 and SiO2 NFs are able to induce both local and systemic toxicity along with microbiota dysbiosis and can be grouped according to the tested fate and hazard descriptors. This supports that the decision nodes of the oral IATAs are suitable for classification and assessment of the toxicity of NFs.
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Affiliation(s)
- Luisana Di Cristo
- Nanoregulatory Platform, Drug Discovery and Development Department, Istituto Italiano Di Tecnologia, 16163 Genova, Italy; (L.D.C.); (C.M.)
| | - Agnes G. Oomen
- National Institute for Public Health and the Environment (RIVM), 3720 Bilthoven, The Netherlands; (A.G.O.); (S.D.)
| | - Susan Dekkers
- National Institute for Public Health and the Environment (RIVM), 3720 Bilthoven, The Netherlands; (A.G.O.); (S.D.)
| | - Colin Moore
- Nanoregulatory Platform, Drug Discovery and Development Department, Istituto Italiano Di Tecnologia, 16163 Genova, Italy; (L.D.C.); (C.M.)
| | - Walter Rocchia
- Computational Modelling of Nanoscale and Biophysical Systems—CONCEPT Lab, Istituto Italiano Di Tecnologia, 16163 Genova, Italy;
| | - Fiona Murphy
- Nano Safety Research Group, School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS, UK; (F.M.); (H.J.J.); (V.S.)
| | - Helinor J. Johnston
- Nano Safety Research Group, School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS, UK; (F.M.); (H.J.J.); (V.S.)
| | - Gemma Janer
- LEITAT Technological Center, 08005 Barcelona, Spain;
| | - Andrea Haase
- Department of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), 10589 Berlin, Germany;
| | - Vicki Stone
- Nano Safety Research Group, School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS, UK; (F.M.); (H.J.J.); (V.S.)
| | - Stefania Sabella
- Nanoregulatory Platform, Drug Discovery and Development Department, Istituto Italiano Di Tecnologia, 16163 Genova, Italy; (L.D.C.); (C.M.)
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12
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Ma Y, Thurecht KJ, Coombes AGA. Development of enteric-coated, biphasic chitosan/HPMC microcapsules for colon-targeted delivery of anticancer drug-loaded nanoparticles. Int J Pharm 2021; 607:121026. [PMID: 34418474 DOI: 10.1016/j.ijpharm.2021.121026] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Revised: 08/14/2021] [Accepted: 08/16/2021] [Indexed: 12/09/2022]
Abstract
Oral delivery of anticancer drug-loaded nanoparticles (NPs) to the colon offers opportunities to improve colorectal cancer (CRC) treatment by increasing the free drug concentration at tumour sites and/or enhancing NP accumulation in tumours. Indomethacin, 5-FU and curcumin, were entrapped separately in Eudragit RS NPs (approximately 10% w/w loading) using nanoprecipitation and incorporated in biphasic chitosan/HPMC microcapsules (MCs) using aerosolisation. The MCs were designed to release NPs primarily in the colon following chitosan breakdown by bacterial enzymes. Around 10% of the drug-loaded NPs was released from MCs in simulated intestinal fluid (SIF) in 6 h and 20% in simulated colon fluid (SCF). Indomethacin release from MCs was absent in simulated gastric fluid (SGF) and restricted to around 10% in SIF and SCF, respectively, demonstrating potential for delivering a large fraction of contained drug to the colon. Curcumin release from NPs or NP-loaded MCs was negligible in SGF, SIF and SCF, revealing opportunities for delivery of curcumin-loaded NPs to the colon for accumulation in tumours. Curcumin-loaded NPs reduced proliferation of human colon adenocarcinoma HT-29 cells by 83% compared with 50% for free curcumin. These findings demonstrate the potential of chitosan/HPMC microcapsules as a colon-specific delivery vehicle for oral nanomedicines directed against colorectal cancer.
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Affiliation(s)
- Yiming Ma
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia; Evonik Industries, Birmingham, AL, USA(1)
| | - Kristofer J Thurecht
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia; Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD 4072, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology and ARC Training Centre for Innovation in Biomedical Imaging Technology, The University of Queensland, St Lucia, QLD 4072, Australia
| | - Allan G A Coombes
- University of Queensland, School of Pharmacy, Pharmacy Australia Centre of Excellence, 20 Cornwall Street, Woolloongabba, Brisbane, QLD 4102, Australia.
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Banerjee A, Shelver WL. Micro- and Nanoplastic-Mediated Pathophysiological Changes in Rodents, Rabbits, and Chickens: A Review. J Food Prot 2021; 84:1480-1495. [PMID: 34347096 DOI: 10.4315/jfp-21-117] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 04/18/2021] [Indexed: 12/14/2022]
Abstract
ABSTRACT Plastics provide tremendous societal benefits and are an indispensable part of our lives. However, fragmented plastics or those intentionally manufactured in small sizes (microplastics and nanoplastics) are of concern because they can infiltrate soils and enter the human food chain through trophic transfer. The pathophysiological impacts of micro- and nanoplastics in humans are not characterized, but their effects in terrestrial mammals may help elucidate their potential effects in humans. Rodent studies have demonstrated that micro- and nanoplastics can breach the intestinal barrier, accumulate in various organs, cause gut dysbosis, decrease mucus secretion, induce metabolic alterations, and cause neurotoxicity, among other pathophysiologic effects. Larger mammals such as rabbits can also absorb microplastics orally. In farm animals such as chickens, microplastics have been detected in the gut, thereby raising food safety concerns. This review mostly focuses on studies conducted to assess effects of micro- and nanoplastic exposure through food and water in terrestrial mammals and farm animals including rodents, rabbits, and chickens; identifies main knowledge gaps; and provides recommendations for further research to understand foodborne micro- and nanoplastic toxicity in humans. HIGHLIGHTS
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Affiliation(s)
- Amrita Banerjee
- U.S. Department of Agriculture, Agricultural Research Service, Edward T. Schafer Agricultural Research Center, Biosciences Research Laboratory, 1616 Albrecht Boulevard N, Fargo, North Dakota 58102, USA
| | - Weilin L Shelver
- U.S. Department of Agriculture, Agricultural Research Service, Edward T. Schafer Agricultural Research Center, Biosciences Research Laboratory, 1616 Albrecht Boulevard N, Fargo, North Dakota 58102, USA
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Bao X, Qian K, Yao P. Insulin- and cholic acid-loaded zein/casein-dextran nanoparticles enhance the oral absorption and hypoglycemic effect of insulin. J Mater Chem B 2021; 9:6234-6245. [PMID: 34328161 DOI: 10.1039/d1tb00806d] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Diabetes mellitus is the most common metabolic disease in the world. Herein, insulin- and cholic acid-loaded zein nanoparticles with dextran surfaces were fabricated to enhance the oral absorptions of insulin in the intestine and in the liver which is the primary action organ of endogenous insulin. In the nanoparticles, zein acted as cement to embed insulin, cholic acid and casein by hydrophobic interactions. The hydrophilic dextran conjugated to casein by the Maillard reaction was located on the nanoparticle surface. The nanoparticles had an insulin loading efficiency of 74.6%, a cholic acid loading efficiency of 55.1% and a hydrodynamic diameter of 267 nm. The dextran significantly increased the disperse stability of the nanoparticles, protected the loaded insulin from hydrolysis in digestive juices, and increased the trans-mucus permeability of the insulin. The embedded cholic acid molecules were consecutively exposed to the surface when the nanoparticles were gradually eroded by proteases. The exposed cholic acid promoted the absorptions of the nanoparticles in the ileum and liver via bile acid transporters. The effect of pretreated lymphatic transport inhibitor cycloheximide revealed that about half of the nanoparticles were transported via the intestinal lymphatic transport pathway and the other half of the nanoparticles were transported via portal blood absorption. The oral pharmacological bioavailability of the nanoparticles in type I diabetic mice was 12.5-20.5%. This study demonstrates that nanoparticles are a promising oral delivery system for insulin.
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Affiliation(s)
- Xiaoyan Bao
- State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Fudan University, Shanghai 200438, China.
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15
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Guo Z, Bai Y, Zhang Z, Mei H, Li J, Pu Y, Zhao N, Gao W, Wu F, He B, Xie J. Thermosensitive polymer hydrogel as a physical shield on colonic mucosa for colitis treatment. J Mater Chem B 2021; 9:3874-3884. [PMID: 33928321 DOI: 10.1039/d1tb00499a] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis (UC), is a chronic disease characterized by diffuse mucosal inflammation limited to the colon. Topical drug delivery systems that could be facilely performed and efficiently retained at colon sites are attractive for clinical IBD treatment. Herein, we report the exploration of an injectable thermosensitive copolymer hydrogel as a topical formulation for IBD treatment and demonstrate its feasibility in UC treatment by shielding ulcer sites from the external environment and being a drug reservoir for sustained release. Poly(aliphatic ester)-based triblock copolymer, poly(dl-lactic acid)-poly(ethylene glycol)-poly(dl-lactic acid) (PDLLA-PEG-PDLLA), adopts the solution state at room temperature yet a gel state at body temperature when the polymer concentration is more than 11%. The gel acts not only as a physical mucosal barrier for protecting ulcer sites from microorganisms like bacteria but also as a mesalazine depot for enhanced drug retention in the colon for localized, sustained drug release. In vivo UC treatment reveals that blank gel as a mucosal protector shows nearly the same treatment effect to mesalazine SR granules. Mesalazine-loaded gel significantly suppresses inflammation and has the best outcomes of indices such as colonic length, mucosal injury index, pathological tissue, and inflammatory factor. The injectable thermosensitive polymer hydrogel represents a novel, robust platform for the efficient treatment of IBD by acting as a physical shield to block out the pro-inflammatory factors as well as a drug depot for enhanced drug retention and controlled delivery.
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Affiliation(s)
- Zhaoyuan Guo
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China.
| | - Yun Bai
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China.
| | - Zhuangzhuang Zhang
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China.
| | - Heng Mei
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China.
| | - Jing Li
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China.
| | - Yuji Pu
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China.
| | - Nan Zhao
- Puliyan (Nanjing) Medical Science & Technology Co. LTD, Nanjing 210042, China
| | - Wenxia Gao
- College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, China
| | - Fang Wu
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China.
| | - Bin He
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China.
| | - Jing Xie
- Department of Stomatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
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EFSA Scientific Committee, More S, Bampidis V, Benford D, Bragard C, Halldorsson T, Hernández‐Jerez A, Hougaard Bennekou S, Koutsoumanis K, Lambré C, Machera K, Naegeli H, Nielsen S, Schlatter J, Schrenk D, Silano (deceased) V, Turck D, Younes M, Castenmiller J, Chaudhry Q, Cubadda F, Franz R, Gott D, Mast J, Mortensen A, Oomen AG, Weigel S, Barthelemy E, Rincon A, Tarazona J, Schoonjans R. Guidance on risk assessment of nanomaterials to be applied in the food and feed chain: human and animal health. EFSA J 2021; 19:e06768. [PMID: 34377190 PMCID: PMC8331059 DOI: 10.2903/j.efsa.2021.6768] [Citation(s) in RCA: 96] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/30/2021] [Indexed: 02/08/2023] Open
Abstract
The EFSA has updated the Guidance on risk assessment of the application of nanoscience and nanotechnologies in the food and feed chain, human and animal health. It covers the application areas within EFSA's remit, including novel foods, food contact materials, food/feed additives and pesticides. The updated guidance, now Scientific Committee Guidance on nano risk assessment (SC Guidance on Nano-RA), has taken account of relevant scientific studies that provide insights to physico-chemical properties, exposure assessment and hazard characterisation of nanomaterials and areas of applicability. Together with the accompanying Guidance on Technical requirements for regulated food and feed product applications to establish the presence of small particles including nanoparticles (Guidance on Particle-TR), the SC Guidance on Nano-RA specifically elaborates on physico-chemical characterisation, key parameters that should be measured, methods and techniques that can be used for characterisation of nanomaterials and their determination in complex matrices. The SC Guidance on Nano-RA also details aspects relating to exposure assessment and hazard identification and characterisation. In particular, nanospecific considerations relating to in vitro/in vivo toxicological studies are discussed and a tiered framework for toxicological testing is outlined. Furthermore, in vitro degradation, toxicokinetics, genotoxicity, local and systemic toxicity as well as general issues relating to testing of nanomaterials are described. Depending on the initial tier results, additional studies may be needed to investigate reproductive and developmental toxicity, chronic toxicity and carcinogenicity, immunotoxicity and allergenicity, neurotoxicity, effects on gut microbiome and endocrine activity. The possible use of read-across to fill data gaps as well as the potential use of integrated testing strategies and the knowledge of modes or mechanisms of action are also discussed. The Guidance proposes approaches to risk characterisation and uncertainty analysis.
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Patra A, Lalhriatpuii M. Progress and Prospect of Essential Mineral Nanoparticles in Poultry Nutrition and Feeding-a Review. Biol Trace Elem Res 2020; 197:233-253. [PMID: 31828724 DOI: 10.1007/s12011-019-01959-1] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Accepted: 10/28/2019] [Indexed: 02/07/2023]
Abstract
Nanobiotechnology is a growing field in animal and veterinary sciences for various practical applications including diagnostic, therapeutic, and nutritional applications. Recently, nanoforms or nanoparticles (NP) of essential minerals have been explored for growth performance, feed utilization, and health status of animals. Various mineral NP, such as calcium, zinc, copper, selenium, and chromium, have been studied in different farm animals including poultry. Because mineral NP are smaller in size, and show different chemical and physical properties, they are usually absorbed in greater amounts from gastrointestinal tract and exert enhanced biological effects in the target tissues of animals. In various studies, mineral NP have been comparatively studied relating to its larger inorganic and organic particles in poultry. There are contradictory findings among the studies on comparative improvement of production performance and other mineral functions perhaps due to different sizes, shapes, and properties of NP, and interactions of minerals present in basal diets. There are not many studies correlating physical and chemical properties of mineral NP and their biological functions in the body. Nonetheless, it appears that mineral NP have potential for their uses as mineral supplements in preference to inorganic mineral supplements for their better absorption avoiding antagonistic interactions with other minerals, growth performance, and physiological functions, especially at lower doses compared with the doses that are recommended for their larger particles. Supplementation of mineral NP in diets could be a promising option in the future. This review summarizes the studies of different essential mineral NP used as mineral supplements for feed intake, growth performance, egg production and quality, and blood variables in poultry.
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Affiliation(s)
- Amlan Patra
- Department of Animal Nutrition, West Bengal University of Animal and Fishery Sciences, 37 K.B. Sarani, Belgachia, Kolkata, 700037, India.
| | - Melody Lalhriatpuii
- National Dairy Research Institute, Eastern Regional Station, Kalyani, West Bengal, India
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18
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Hydrogel Formulations Incorporating Drug Nanocrystals Enhance the Therapeutic Effect of Rebamipide in a Hamster Model for Oral Mucositis. Pharmaceutics 2020; 12:pharmaceutics12060532. [PMID: 32527029 PMCID: PMC7356607 DOI: 10.3390/pharmaceutics12060532] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 06/07/2020] [Accepted: 06/08/2020] [Indexed: 12/20/2022] Open
Abstract
A mouthwash formulation of rebamipide (REB) is commonly used to treat oral mucositis; however, this formulation does not provide sufficient treatment or prevention in cases of serious oral mucositis. To improve treatment, we attempted to design a hydrogel incorporating REB nanocrystals (R-NPs gel). The R-NPs gel was prepared by a bead mill method using carbopol hydrogel, methylcellulose and 2-hydroxypropyl-β-cyclodextrin, and another hydrogel incorporating REB microcrystals (R-MPs gel) was prepared following the same protocol but without the bead mill treatment. The REB particle size in the R-MPs gel was 0.15–25 μm, and while the REB particle size was 50–180 nm in the R-NPs gel. Next, we investigated the therapeutic effect of REB nanocrystals on oral mucositis using a hamster model. Almost all of the REB was released as drug nanocrystals from the R-NPs gel, and the REB content in the cheek pouch of hamsters treated with R-NPs gel was significantly higher than that of hamsters treated with R-MPs gel. Further, treatment with REB hydrogels enhanced the healing of oral wounds in the hamsters. REB accumulation in the cheek pouch of hamsters treated with the R-NPs gel was prevented by an inhibitor of clathrin-dependent endocytosis (CME) (40 μM dynasore). In conclusion, we designed an R-NPs gel and found that REB nanocrystals are taken up by tissues through CME, where they provide a persistent effect resulting in an enhancement of oral wound healing.
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Wang X, Zheng H, Zhao J, Luo X, Wang Z, Xing B. Photodegradation Elevated the Toxicity of Polystyrene Microplastics to Grouper ( Epinephelus moara) through Disrupting Hepatic Lipid Homeostasis. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2020; 54:6202-6212. [PMID: 32207945 DOI: 10.1021/acs.est.9b07016] [Citation(s) in RCA: 162] [Impact Index Per Article: 32.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
Microplastics (MPs) have caused increasing global concerns due to their detrimental effects on marine ecosystems. However, the role of photodegradation in altering toxicity of MPs to marine organisms is poorly understood. We therefore investigated the photolytic transformation of pristine polystyrene fragments (P-PS) by 60-day ultraviolet (UV) irradiation, and compared the toxicity of P-PS, photodegraded PS (PD-PS), and commercially available polystyrene microbeads (C-PS) to juvenile grouper (Epinephelus moara). Photodegradation reduced the size from ∼55.9 μm of P-PS to ∼38.6 μm of PD-PS, even produced nanoparticles (∼75 nm) with a yield of 7.03 ± 0.37% (w/w), and induced surface oxidation and formation of persistent free radicals (e.g., CO•, COO•). Also, endogenous pollutants (chemical additives and polymer fragments) were leached out. Thus, PD-PS had the highest growth inhibition and lipidosis-driven hepatic lesions of grouper, followed by P-PS and C-PS, which was mainly explained by increased hepatic bioaccumulation of MPs/NPs and released endogenous toxicants. Furthermore, oxidative stress-triggered mitochondrial depolarization, suppression of fatty acid oxidation and transport, and promotion of inflammation were identified as the key mechanisms for the enhanced hepatotoxicity after photodegradation. This work provides new insight into the potential hazard and harm of MPs in marine environments after photodegradation.
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Affiliation(s)
- Xiao Wang
- Institute of Coastal Environmental Pollution Control, Key Laboratory of Marine Environment and Ecology, Ministry of Education, Institute for Advanced Ocean Study, Ocean University of China, Qingdao 266100 China
| | - Hao Zheng
- Institute of Coastal Environmental Pollution Control, Key Laboratory of Marine Environment and Ecology, Ministry of Education, Institute for Advanced Ocean Study, Ocean University of China, Qingdao 266100 China
- Laboratory for Marine Ecology and Environmental Science, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China
| | - Jian Zhao
- Institute of Coastal Environmental Pollution Control, Key Laboratory of Marine Environment and Ecology, Ministry of Education, Institute for Advanced Ocean Study, Ocean University of China, Qingdao 266100 China
- Laboratory for Marine Ecology and Environmental Science, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China
| | - Xianxiang Luo
- Institute of Coastal Environmental Pollution Control, Key Laboratory of Marine Environment and Ecology, Ministry of Education, Institute for Advanced Ocean Study, Ocean University of China, Qingdao 266100 China
- Laboratory for Marine Ecology and Environmental Science, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China
| | - Zhenyu Wang
- Institute of Environmental Processes and Pollution Control, and School of Environmental and Civil Engineering, Jiangnan University, Wuxi 214122, China
| | - Baoshan Xing
- Stockbridge School of Agriculture, University of Massachusetts, Amherst, Massachusetts 01003, United States
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20
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Prata JC, da Costa JP, Lopes I, Duarte AC, Rocha-Santos T. Environmental exposure to microplastics: An overview on possible human health effects. THE SCIENCE OF THE TOTAL ENVIRONMENT 2020; 702:134455. [PMID: 31733547 DOI: 10.1016/j.scitotenv.2019.134455] [Citation(s) in RCA: 1019] [Impact Index Per Article: 203.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Revised: 08/26/2019] [Accepted: 09/13/2019] [Indexed: 04/14/2023]
Abstract
Microplastics are ubiquitous environmental contaminants leading to inevitable human exposure. Even so, little is known about the effects of microplastics in human health. Thus, in this work we review the evidence for potential negative effects of microplastics in the human body, focusing on pathways of exposure and toxicity. Exposure may occur by ingestion, inhalation and dermal contact due to the presence of microplastics in products, foodstuff and air. In all biological systems, microplastic exposure may cause particle toxicity, with oxidative stress, inflammatory lesions and increased uptake or translocation. The inability of the immune system to remove synthetic particles may lead to chronic inflammation and increase risk of neoplasia. Furthermore, microplastics may release their constituents, adsorbed contaminants and pathogenic organisms. Nonetheless, knowledge on microplastic toxicity is still limited and largely influenced by exposure concentration, particle properties, adsorbed contaminants, tissues involved and individual susceptibility, requiring further research.
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Affiliation(s)
- Joana Correia Prata
- Centre for Environmental and Marine Studies (CESAM) & Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
| | - João P da Costa
- Centre for Environmental and Marine Studies (CESAM) & Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
| | - Isabel Lopes
- Centre for Environmental and Marine Studies (CESAM) & Department of Biology, University of Aveiro, 3810-193 Aveiro, Portugal.
| | - Armando C Duarte
- Centre for Environmental and Marine Studies (CESAM) & Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
| | - Teresa Rocha-Santos
- Centre for Environmental and Marine Studies (CESAM) & Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
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Wang X, Liu L, Zheng H, Wang M, Fu Y, Luo X, Li F, Wang Z. Polystyrene microplastics impaired the feeding and swimming behavior of mysid shrimp Neomysis japonica. MARINE POLLUTION BULLETIN 2020; 150:110660. [PMID: 31727317 DOI: 10.1016/j.marpolbul.2019.110660] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 10/09/2019] [Accepted: 10/09/2019] [Indexed: 06/10/2023]
Abstract
Growing evidences revealed the deleterious impacts of microplastics (MPs) on marine organisms. However, the effects of MPs on the movement behavior of marine crustacean is poorly understood. Therefore, this study aims to evaluate the physiological and behavioral responses of mysid shrimp (Neomysis japonica) larvae to polystyrene (PS) and carboxylated polystyrene (PS-COOH). PS-COOH presented a greater physiological toxicity to shrimp larvae compared to PS, causing significant lethal and growth inhibition effect, owing to bioaccumulation of MPs inside stomach. Both two MPs decreased the feeding efficiency of larvae, showing weakened predation competence. Moreover, reduced hunting and/or explorative ability of shrimps caused by MPs was also identified, which was evidenced by an overall decrease in swimming activity, range and frequency after exposure. Our study firstly highlighted that micron-sized polystyrene particles had the negative effects on the movement behavior of mysid shrimp larvae, thus posing potential hazard to population dynamics and ecological function of marine crustacean.
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Affiliation(s)
- Xiao Wang
- Institute of Coastal Environmental Pollution Control, Key Laboratory of Marine Environment and Ecology, Ministry of Education, Institute for Advanced Ocean Study, Ocean University of China, Qingdao, 266100, China
| | - Liuqingqing Liu
- Institute of Coastal Environmental Pollution Control, Key Laboratory of Marine Environment and Ecology, Ministry of Education, Institute for Advanced Ocean Study, Ocean University of China, Qingdao, 266100, China
| | - Hao Zheng
- Institute of Coastal Environmental Pollution Control, Key Laboratory of Marine Environment and Ecology, Ministry of Education, Institute for Advanced Ocean Study, Ocean University of China, Qingdao, 266100, China; Laboratory for Marine Ecology and Environmental Science, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China.
| | - Mingxin Wang
- Institute of Coastal Environmental Pollution Control, Key Laboratory of Marine Environment and Ecology, Ministry of Education, Institute for Advanced Ocean Study, Ocean University of China, Qingdao, 266100, China
| | - Yuanxin Fu
- Institute of Coastal Environmental Pollution Control, Key Laboratory of Marine Environment and Ecology, Ministry of Education, Institute for Advanced Ocean Study, Ocean University of China, Qingdao, 266100, China
| | - Xianxiang Luo
- Institute of Coastal Environmental Pollution Control, Key Laboratory of Marine Environment and Ecology, Ministry of Education, Institute for Advanced Ocean Study, Ocean University of China, Qingdao, 266100, China; Laboratory for Marine Ecology and Environmental Science, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China
| | - Fengmin Li
- Institute of Coastal Environmental Pollution Control, Key Laboratory of Marine Environment and Ecology, Ministry of Education, Institute for Advanced Ocean Study, Ocean University of China, Qingdao, 266100, China; Laboratory for Marine Ecology and Environmental Science, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China
| | - Zhenyu Wang
- Institute of Environmental Processes and Pollution Control, School of Environmental and Civil Engineering, Jiangnan University, Wuxi, 214122, China.
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Wang P, Cao X, Chu Y, Wang P. Ginkgolides-loaded soybean phospholipid-stabilized nanosuspension with improved storage stability and in vivo bioavailability. Colloids Surf B Biointerfaces 2019; 181:910-917. [PMID: 31382340 DOI: 10.1016/j.colsurfb.2019.06.050] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Revised: 05/31/2019] [Accepted: 06/22/2019] [Indexed: 10/26/2022]
Abstract
The purpose of this study was to investigate the effects of soybean phospholipid, as a steric stabilizer, on improving dissolution rate, storage stability and bioavailability of ginkgolides. The ginkgolides coarse powder, hydroxypropyl methylcellulose (HPMC), soybean phospholipid and sodium dodecyl sulfate (SDS) were mixed and wet-milled to prepare nanosuspension S1. Nanosuspension S2 was obtained by the same technique except adding the soybean phospholipid. Results of particle size showed that particle size (D50) of S1 significantly decreased from 44.25 μm to 0.373 μm. Results of differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and transmission electron microscope (TEM) showed that ginkgolides in nanosuspension still maintained its crystallinity, and the nanoparticles were all nearly circular and uniformly dispersed. Then, pellets F1 and F2 were prepared by layering S1 and S2 onto the microcrystalline cellulose (MCC) spheres, respectively. The dissolution rate of ginkgolide A (GA) and ginkgolide B (GB) in F1 was 98.3% and 97.7% in 30 min, respectively. It was much higher than F2 (89.0% and 86.5%) and coarse powder of ginkgolides (22.3% and 24.6%). According to the results of stability test, the storage stability of F1 was improved compared with F2. In addition, compared with coarse powder of ginkgolides, the relative bioavailability of GA and GB in F1 were up to (221.84 ± 106.67) % and (437.45 ± 336.43) %, respectively. The above results demonstrated that soybean phospholipid added to the nanosuspension played an important role in improving drug dissolution rate, storage stability and in vivo bioavailability: (1) The amphiphilic soybean phospholipid interacted with the drug, with the hydrophobic part adsorbed on the surface of the poorly soluble drug and the hydrophilic part exposed to the aqueous medium. This increases the wettability of the nanoparticles, which ensure a good redispersibility of the drug particles. (2) It could self-assemble to form an interfacial phospholipid film by surrounding the individual nanoparticles, which can produce enough steric hindrance to prevent nanoparticles from aggregation and ensure a rapid dissolution rate. (3) Soybean phospholipid and its hydrolysate formed strong micellar solubilizing vehicles with bile salts in vivo, stimulated the absorption process of ginkgolides. Thus, soybean phospholipid was a promising steric stabilizer in nanosuspension drug delivery system.
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Affiliation(s)
- Puxiu Wang
- Department of Pharmacy, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, PR China.
| | - Xiuxiu Cao
- School of Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning, PR China.
| | - Yang Chu
- Department of Pharmacy, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, PR China.
| | - Puxiu Wang
- Department of Pharmacy, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, PR China.
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Nanoparticles capture on cellulose nanofiber depth filters. Carbohydr Polym 2018; 201:482-489. [DOI: 10.1016/j.carbpol.2018.07.068] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Revised: 07/18/2018] [Accepted: 07/24/2018] [Indexed: 11/20/2022]
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Abstract
Phenolic compounds, while widely recognized for their biological potential, when added into food matrixes may interact with food constituents. One example of this is the interaction between phenolic compounds and proteins, that may result in the formation of complexes and alter the bioavailability of both phenolic compounds and the nutrient availability. Moreover, when adding compounds to improve the functionality of a food matrix, these interactions may compromise the perceived benefits of the additions. Nanoencapsulation has been considered one of the means to circumvent these interactions, as they may function as a physical barrier between the phenolic compounds and the matrix (preventing not only the loss of bioactivity, but eventual sensorial alterations of the foods), protect phenolic compounds through the gastrointestinal tract, and may enhance phenolic absorption through cellular endocytosis. However, despite these advantages the food industry is still limited in its nanotechnological solutions, as special care must be taken to use food-grade encapsulants which will not pose any deleterious effect towards human health. Therefore, this review aims to provide an encompassing view of the existing advantages and limitations of nanotechnology, associated with the inclusion of phenolic compounds in dairy beverages.
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Hardy A, Benford D, Halldorsson T, Jeger MJ, Knutsen HK, More S, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Schlatter JR, Silano V, Solecki R, Turck D, Younes M, Chaudhry Q, Cubadda F, Gott D, Oomen A, Weigel S, Karamitrou M, Schoonjans R, Mortensen A. Guidance on risk assessment of the application of nanoscience and nanotechnologies in the food and feed chain: Part 1, human and animal health. EFSA J 2018; 16:e05327. [PMID: 32625968 PMCID: PMC7009542 DOI: 10.2903/j.efsa.2018.5327] [Citation(s) in RCA: 124] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
The European Food Safety Authority has produced this Guidance on human and animal health aspects (Part 1) of the risk assessment of nanoscience and nanotechnology applications in the food and feed chain. It covers the application areas within EFSA's remit, e.g. novel foods, food contact materials, food/feed additives and pesticides. The Guidance takes account of the new developments that have taken place since publication of the previous Guidance in 2011. Potential future developments are suggested in the scientific literature for nanoencapsulated delivery systems and nanocomposites in applications such as novel foods, food/feed additives, biocides, pesticides and food contact materials. Therefore, the Guidance has taken account of relevant new scientific studies that provide more insights to physicochemical properties, exposure assessment and hazard characterisation of nanomaterials. It specifically elaborates on physicochemical characterisation of nanomaterials in terms of how to establish whether a material is a nanomaterial, the key parameters that should be measured, the methods and techniques that can be used for characterisation of nanomaterials and their determination in complex matrices. It also details the aspects relating to exposure assessment and hazard identification and characterisation. In particular, nanospecific considerations relating to in vivo/in vitro toxicological studies are discussed and a tiered framework for toxicological testing is outlined. It describes in vitro degradation, toxicokinetics, genotoxicity as well as general issues relating to testing of nanomaterials. Depending on the initial tier results, studies may be needed to investigate reproductive and developmental toxicity, immunotoxicity, allergenicity, neurotoxicity, effects on gut microbiome and endocrine activity. The possible use of read‐across to fill data gaps as well as the potential use of integrated testing strategies and the knowledge of modes/mechanisms of action are also discussed. The Guidance proposes approaches to risk characterisation and uncertainty analysis, and provides recommendations for further research in this area. This publication is linked to the following EFSA Supporting Publications article: http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2018.EN-1430/full
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Takeuchi I, Kamiki Y, Makino K. Therapeutic efficacy of rebamipide-loaded PLGA nanoparticles coated with chitosan in a mouse model for oral mucositis induced by cancer chemotherapy. Colloids Surf B Biointerfaces 2018; 167:468-473. [PMID: 29723818 DOI: 10.1016/j.colsurfb.2018.04.047] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2018] [Revised: 04/23/2018] [Accepted: 04/24/2018] [Indexed: 12/31/2022]
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Ganguly P, Breen A, Pillai SC. Toxicity of Nanomaterials: Exposure, Pathways, Assessment, and Recent Advances. ACS Biomater Sci Eng 2018; 4:2237-2275. [DOI: 10.1021/acsbiomaterials.8b00068] [Citation(s) in RCA: 126] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Priyanka Ganguly
- Nanotechnology and Bio-Engineering Research Group, Department of Environmental Science, School of Science, Institute of Technology Sligo, Ash Lane, Sligo F91 YW50, Ireland
- Centre for Precision Engineering, Materials and Manufacturing Research (PEM), Institute of Technology Sligo, Ash Lane, Sligo F91 YW50, Ireland
| | - Ailish Breen
- Nanotechnology and Bio-Engineering Research Group, Department of Environmental Science, School of Science, Institute of Technology Sligo, Ash Lane, Sligo F91 YW50, Ireland
- Centre for Precision Engineering, Materials and Manufacturing Research (PEM), Institute of Technology Sligo, Ash Lane, Sligo F91 YW50, Ireland
| | - Suresh C. Pillai
- Nanotechnology and Bio-Engineering Research Group, Department of Environmental Science, School of Science, Institute of Technology Sligo, Ash Lane, Sligo F91 YW50, Ireland
- Centre for Precision Engineering, Materials and Manufacturing Research (PEM), Institute of Technology Sligo, Ash Lane, Sligo F91 YW50, Ireland
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Kootala S, Filho L, Srivastava V, Linderberg V, Moussa A, David L, Trombotto S, Crouzier T. Reinforcing Mucus Barrier Properties with Low Molar Mass Chitosans. Biomacromolecules 2018; 19:872-882. [PMID: 29451983 DOI: 10.1021/acs.biomac.7b01670] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The mucus gel covers the wet epithelia that forms the inner lining of the body. It constitutes our first line of defense protecting the body from infections and other deleterious molecules. Failure of the mucus barrier can lead to the inflammation of the mucosa such as in inflammatory bowel diseases. Unfortunately, there are no effective strategies that reinforce the mucus barrier properties to recover or enhance its ability to protect the epithelium. Herein, we describe a mucus engineering approach that addresses this issue where we physically cross-link the mucus gel with low molar mass chitosan variants to reinforce its barrier functions. We tested the effect of these chitosans on mucus using in-lab purified porcine gastric mucins, which mimic the native properties of mucus, and on mucus-secreting HT29-MTX epithelial cell cultures. We found that the lowest molar mass chitosan variant (degree of polymerization of 8) diffuses deep into the mucus gels while physically cross-linking the mucin polymers, whereas the higher molar mass chitosan variants (degree of polymerization of 52 and 100) interact only superficially. The complexation resulted in a tighter mucin polymer mesh that slowed the diffusion of dextran polymers and of the cholera toxin B subunit protein through the mucus gels. These results uncover a new use for low molar mass mucoadhesive polymers such as chitosans as noncytotoxic mucosal barrier enhancers that could be valuable in the prevention and treatment of mucosal diseases.
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Affiliation(s)
- Sujit Kootala
- KTH Royal Institute of Technology, School of Engineering Sciences in Chemistry, Biotechnology and Health, Department of Chemistry , Division of Glycoscience , SE-100 44 Stockholm , Sweden
| | - Luimar Filho
- Department of Engineering Sciences, Applied Materials Science , Uppsala University , 752 37 Uppsala , Sweden
| | - Vaibhav Srivastava
- KTH Royal Institute of Technology, School of Engineering Sciences in Chemistry, Biotechnology and Health, Department of Chemistry , Division of Glycoscience , SE-100 44 Stockholm , Sweden
| | - Victoria Linderberg
- KTH Royal Institute of Technology, School of Engineering Sciences in Chemistry, Biotechnology and Health, Department of Chemistry , Division of Glycoscience , SE-100 44 Stockholm , Sweden
| | - Amani Moussa
- Ingénierie des Matériaux Polymères (IMP), CNRS UMR 5223 , Université Claude Bernard Lyon 1, Univ Lyon , 69622 Villeurbanne , France
| | - Laurent David
- Ingénierie des Matériaux Polymères (IMP), CNRS UMR 5223 , Université Claude Bernard Lyon 1, Univ Lyon , 69622 Villeurbanne , France
| | - Stéphane Trombotto
- Ingénierie des Matériaux Polymères (IMP), CNRS UMR 5223 , Université Claude Bernard Lyon 1, Univ Lyon , 69622 Villeurbanne , France
| | - Thomas Crouzier
- KTH Royal Institute of Technology, School of Engineering Sciences in Chemistry, Biotechnology and Health, Department of Chemistry , Division of Glycoscience , SE-100 44 Stockholm , Sweden
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Lichtenstein D, Meyer T, Böhmert L, Juling S, Fahrenson C, Selve S, Thünemann A, Meijer J, Estrela-Lopis I, Braeuning A, Lampen A. Dosimetric Quantification of Coating-Related Uptake of Silver Nanoparticles. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2017; 33:13087-13097. [PMID: 28918629 DOI: 10.1021/acs.langmuir.7b01851] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/18/2023]
Abstract
The elucidation of mechanisms underlying the cellular uptake of nanoparticles (NPs) is an important topic in nanotoxicological research. Most studies dealing with silver NP uptake provide only qualitative data about internalization efficiency and do not consider NP-specific dosimetry. Therefore, we performed a comprehensive comparison of the cellular uptake of differently coated silver NPs of comparable size in different human intestinal Caco-2 cell-derived models to cover also the influence of the intestinal mucus barrier and uptake-specialized M-cells. We used a combination of the Transwell system, transmission electron microscopy, atomic absorption spectroscopy, and ion beam microscopy techniques. The computational in vitro sedimentation, diffusion, and dosimetry (ISDD) model was used to determine the effective dose of the particles in vitro based on their individual physicochemical characteristics. Data indicate that silver NPs with a similar size and shape show coating-dependent differences in their uptake into Caco-2 cells. The internalization of silver NPs was enhanced in uptake-specialized M-cells while the mucus did not provide a substantial barrier for NP internalization. ISDD modeling revealed a fivefold underestimation of dose-response relationships of NPs in in vitro assays. In summary, the present study provides dosimetry-adjusted quantitative data about the influence of NP coating materials in cellular uptake into human intestinal cells. Underestimation of particle effects in vitro might be prevented by using dosimetry models and by considering cell models with greater proximity to the in vivo situation, such as the M-cell model.
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Affiliation(s)
- Dajana Lichtenstein
- Department of Food Safety, German Federal Institute for Risk Assessment , Max-Dohrn-Str. 8-10, 10589 Berlin, Germany
| | - Thomas Meyer
- Institute for Medical Physics and Biophysics, Leipzig University , Härtelstraße 16-18, 04107 Leipzig, Germany
| | - Linda Böhmert
- Department of Food Safety, German Federal Institute for Risk Assessment , Max-Dohrn-Str. 8-10, 10589 Berlin, Germany
| | - Sabine Juling
- Department of Food Safety, German Federal Institute for Risk Assessment , Max-Dohrn-Str. 8-10, 10589 Berlin, Germany
| | - Christoph Fahrenson
- ZELMI, Technical University Berlin , Straße des 17. Juni 135, 10623 Berlin, Germany
| | - Sören Selve
- ZELMI, Technical University Berlin , Straße des 17. Juni 135, 10623 Berlin, Germany
| | - Andreas Thünemann
- German Federal Institute for Materials Research and Testing , Unter den Eichen 87, 12205 Berlin, Germany
| | - Jan Meijer
- Nuclear Solid State Physics, Leipzig University , Linnéstraße 5, 04103 Leipzig, Germany
| | - Irina Estrela-Lopis
- Institute for Medical Physics and Biophysics, Leipzig University , Härtelstraße 16-18, 04107 Leipzig, Germany
| | - Albert Braeuning
- Department of Food Safety, German Federal Institute for Risk Assessment , Max-Dohrn-Str. 8-10, 10589 Berlin, Germany
| | - Alfonso Lampen
- Department of Food Safety, German Federal Institute for Risk Assessment , Max-Dohrn-Str. 8-10, 10589 Berlin, Germany
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30
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Biopolymer Composite Materials with Antimicrobial Effects Applied to the Food Industry. ACTA ACUST UNITED AC 2017. [DOI: 10.1007/978-3-319-66417-0_3] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Collard F, Gilbert B, Compère P, Eppe G, Das K, Jauniaux T, Parmentier E. Microplastics in livers of European anchovies (Engraulis encrasicolus, L.). ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2017; 229:1000-1005. [PMID: 28768577 DOI: 10.1016/j.envpol.2017.07.089] [Citation(s) in RCA: 257] [Impact Index Per Article: 32.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/05/2017] [Revised: 07/25/2017] [Accepted: 07/25/2017] [Indexed: 05/21/2023]
Abstract
Microplastics (MPs) are thought to be ingested by a wide range of marine organisms before being excreted. However, several studies in marine organisms from different taxa have shown that MPs and nanoplastics could be translocated in other organs. In this study, we investigated the presence of MPs in the livers of commercial zooplanktivorous fishes collected in the field. The study focuses mainly on the European anchovy Engraulis encrasicolus but concerns also the European pilchard Sardina pilchardus and the Atlantic herring Clupea harengus. Two complementary methodologies were used to attest the occurrence of MPs in the hepatic tissue and to exclude contamination. 1) MPs were isolated by degradation of the hepatic tissue. 2) Cryosections were made on the livers and observed in polarized light microscopy. Both methods separately revealed that MPs, mainly polyethylene (PE), were translocated into the livers of the three clupeid species. In anchovy, 80 per cent of livers contained relatively large MPs that ranged from 124 μm to 438 μm, showing a high level of contamination. Two translocation pathways are hypothesized: (i) large particles found in the liver resulted from the agglomeration of smaller pieces, and/or (ii) they simply pass through the intestinal barrier. Further studies are however required to understand the exact process.
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Affiliation(s)
- France Collard
- Laboratory of Functional and Evolutionary Morphology, B6c, Department of Biology, Ecology and Evolution, AFFISH-RC, University of Liege, 4000 Liege, Belgium; Laboratory of Oceanology - MARE Center, B6c, Department of Biology, Ecology and Evolution, University of Liege, 4000 Liege, Belgium.
| | - Bernard Gilbert
- Inorganic Analytical Chemistry Laboratory, B6c, Department of Chemistry, University of Liege, 4000 Liege, Belgium
| | - Philippe Compère
- Laboratory of Functional and Evolutionary Morphology, B6c, Department of Biology, Ecology and Evolution, AFFISH-RC, University of Liege, 4000 Liege, Belgium
| | - Gauthier Eppe
- Inorganic Analytical Chemistry Laboratory, B6c, Department of Chemistry, University of Liege, 4000 Liege, Belgium
| | - Krishna Das
- Laboratory of Oceanology - MARE Center, B6c, Department of Biology, Ecology and Evolution, University of Liege, 4000 Liege, Belgium
| | - Thierry Jauniaux
- Department of Veterinary Pathology, B43, Fundamental and Applied Research for Animals & Health (FARAH), University of Liege, 4000 Liege, Belgium
| | - Eric Parmentier
- Laboratory of Functional and Evolutionary Morphology, B6c, Department of Biology, Ecology and Evolution, AFFISH-RC, University of Liege, 4000 Liege, Belgium.
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Abstract
Microplastics are a pollutant of environmental concern. Their presence in food destined for human consumption and in air samples has been reported. Thus, microplastic exposure via diet or inhalation could occur, the human health effects of which are unknown. The current review article draws upon cross-disciplinary scientific literature to discuss and evaluate the potential human health impacts of microplastics and outlines urgent areas for future research. Key literature up to September 2016 relating to accumulation, particle toxicity, and chemical and microbial contaminants was critically examined. Although microplastics and human health is an emerging field, complementary existing fields indicate potential particle, chemical and microbial hazards. If inhaled or ingested, microplastics may accumulate and exert localized particle toxicity by inducing or enhancing an immune response. Chemical toxicity could occur due to the localized leaching of component monomers, endogenous additives, and adsorbed environmental pollutants. Chronic exposure is anticipated to be of greater concern due to the accumulative effect that could occur. This is expected to be dose-dependent, and a robust evidence-base of exposure levels is currently lacking. Although there is potential for microplastics to impact human health, assessing current exposure levels and burdens is key. This information will guide future research into the potential mechanisms of toxicity and hence therein possible health effects.
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Affiliation(s)
- Stephanie L Wright
- MRC-PHE Centre for Environment and Health, Analytical and Environmental Sciences, King's College London , London SE1 9NH, United Kingdom
| | - Frank J Kelly
- MRC-PHE Centre for Environment and Health, Analytical and Environmental Sciences, King's College London , London SE1 9NH, United Kingdom
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Mackie AR, Goycoolea FM, Menchicchi B, Caramella CM, Saporito F, Lee S, Stephansen K, Chronakis IS, Hiorth M, Adamczak M, Waldner M, Nielsen HM, Marcelloni L. Innovative Methods and Applications in Mucoadhesion Research. Macromol Biosci 2017; 17. [DOI: 10.1002/mabi.201600534] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Revised: 02/10/2017] [Indexed: 01/03/2023]
Affiliation(s)
- Alan R. Mackie
- Institute of Food Research; Norwich Research Park Norwich NR4 7UA UK
- School of Food Science and Nutrition; University of Leeds; LS2 9JT Leeds UK
| | - Francisco M. Goycoolea
- School of Food Science and Nutrition; University of Leeds; LS2 9JT Leeds UK
- Institut für Biologie und Biotechnologie der Pflanzen; Westfälische Wilhelms-Universität Münster; Schlossgarten 3 48149 Münster Germany
| | - Bianca Menchicchi
- Department of Medicine 1; University of Erlangen-Nueremberg; Hartmanstrasse 14 91052 Erlangen Germany
- Nanotechnology Group; Department of Plant Biology and Biotechnology; University of Münster; Schlossgarten 3 48149 Münster Germany
| | | | - Francesca Saporito
- Department of Drug Sciences; University of Pavia; Via Taramelli, 12 27100 Pavia Italy
| | - Seunghwan Lee
- Department of Mechanical Engineering; Technical University of Denmark; Produktionstorvet 2800 Kgs Lyngby Copenhagen Denmark
| | - Karen Stephansen
- National Food Institute; Technical University of Denmark; Søltofts Plads, 2800 Kgs Lyngby Copenhagen Denmark
| | - Ioannis S. Chronakis
- National Food Institute; Technical University of Denmark; Søltofts Plads, 2800 Kgs Lyngby Copenhagen Denmark
| | - Marianne Hiorth
- School of Pharmacy; University of Oslo; Postboks 1068 Blindern 0316 OSLO Norway
| | - Malgorzata Adamczak
- School of Pharmacy; University of Oslo; Postboks 1068 Blindern 0316 OSLO Norway
| | - Max Waldner
- Medizinische Klinik 1; Ulmenweg 18 91054 Erlangen Germany
| | - Hanne Mørck Nielsen
- Department of Pharmacy; University of Copenhagen; Universitetsparken 2 2100 Copenhagen Denmark
| | - Luciano Marcelloni
- S.I.I.T. S.r.l Pharmaceutical & Health Food Supplements; Via Canova 5/7-20090 Trezzano S/N Milan Italy
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34
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Gangadoo S, Stanley D, Hughes RJ, Moore RJ, Chapman J. Nanoparticles in feed: Progress and prospects in poultry research. Trends Food Sci Technol 2016. [DOI: 10.1016/j.tifs.2016.10.013] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Abstract
Matters when converted into nanosize provide some unique surface properties, which are different from those of the bulk materials. Nanomaterials show some extraordinary behavioral patterns because of those properties, such as supermagnetism, quantum confinement, etc. A great deal of implication of nanomaterials in nanomedicine has already been realized. Utility of nanomaterials as drug nanocarrier projects many potential advantages of them in drug delivery. Despite many such advantages, the potential risk of health and environmental hazards related to them cannot be ignored. Here various physicochemical factors, such as chemical nature, degradability, surface properties, surface charge, particle size, and shape, have been shown to play a crucial role in toxicity related to drug nanocarriers. Evidence-based findings of some drug nanocarriers have been incorporated to provide distinct knowledge to the readers in the field. A glimpse of current regulatory controls and measures required to combat the challenges of toxicological aspects of drug nanocarriers have been described.
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Abstract
Nanomaterials, including nanoparticles and nanoobjects, are being incorporated into everyday products at an increasing rate. These products include consumer products of interest to toxicologists such as pharmaceuticals, cosmetics, food, food packaging, household products, and so on. The manufacturing of products containing or utilizing nanomaterials in their composition may also present potential toxicologic concerns in the workplace. The molecular complexity and composition of these nanomaterials are ever increasing, and the means and methods being applied to characterize and perform useful toxicologic assessments are rapidly advancing. This article includes presentations by experienced toxicologists in the nanotoxicology community who are focused on the applied aspect of the discipline toward supporting state of the art toxicologic assessments for food products and packaging, pharmaceuticals and medical devices, inhaled nanoparticle and gastrointestinal exposures, and addressing occupational safety and health issues and concerns. This symposium overview article summarizes 5 talks that were presented at the 35th Annual meeting of the American College of Toxicology on the subject of "Applied Nanotechnology."
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Affiliation(s)
| | | | - Anna A Shvedova
- CDC-National Institute for Occupational Safety and Health, Morgantown, WV, USA
| | | | | | - Robin C Guy
- Robin Guy Consulting LLC, Lake Forest, IL, USA
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37
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Bellmann S, Carlander D, Fasano A, Momcilovic D, Scimeca JA, Waldman WJ, Gombau L, Tsytsikova L, Canady R, Pereira DIA, Lefebvre DE. Mammalian gastrointestinal tract parameters modulating the integrity, surface properties, and absorption of food-relevant nanomaterials. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2015; 7:609-22. [PMID: 25641962 PMCID: PMC4949541 DOI: 10.1002/wnan.1333] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Revised: 12/12/2014] [Accepted: 12/15/2014] [Indexed: 12/12/2022]
Abstract
Many natural chemicals in food are in the nanometer size range, and the selective uptake of nutrients with nanoscale dimensions by the gastrointestinal (GI) tract is a normal physiological process. Novel engineered nanomaterials (NMs) can bring various benefits to food, e.g., enhancing nutrition. Assessing potential risks requires an understanding of the stability of these entities in the GI lumen, and an understanding of whether or not they can be absorbed and thus become systemically available. Data are emerging on the mammalian in vivo absorption of engineered NMs composed of chemicals with a range of properties, including metal, mineral, biochemical macromolecules, and lipid-based entities. In vitro and in silico fluid incubation data has also provided some evidence of changes in particle stability, aggregation, and surface properties following interaction with luminal factors present in the GI tract. The variables include physical forces, osmotic concentration, pH, digestive enzymes, other food, and endogenous biochemicals, and commensal microbes. Further research is required to fill remaining data gaps on the effects of these parameters on NM integrity, physicochemical properties, and GI absorption. Knowledge of the most influential luminal parameters will be essential when developing models of the GI tract to quantify the percent absorption of food-relevant engineered NMs for risk assessment.
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Affiliation(s)
| | | | - Alessio Fasano
- Massachusetts General Hospital for Children, Harvard Medical School, Boston, MA, USA
| | - Dragan Momcilovic
- Department of Health and Human Services, US Food and Drug Administration, Silver Spring, MD, USA
| | | | | | | | - Lyubov Tsytsikova
- Center for Risk Science Innovation and Application, ILSI Research Foundation, Washington, DC, USA
| | - Richard Canady
- Center for Risk Science Innovation and Application, ILSI Research Foundation, Washington, DC, USA
| | - Dora I A Pereira
- MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK
| | - David E Lefebvre
- Regulatory Toxicology Research Division, Food Directorate, Health Canada, Ottawa, Canada
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38
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Duffy CV, David L, Crouzier T. Covalently-crosslinked mucin biopolymer hydrogels for sustained drug delivery. Acta Biomater 2015; 20:51-59. [PMID: 25818947 DOI: 10.1016/j.actbio.2015.03.024] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2014] [Revised: 02/24/2015] [Accepted: 03/21/2015] [Indexed: 12/11/2022]
Abstract
The sustained delivery of both hydrophobic and hydrophilic drugs from hydrogels has remained a challenge requiring the design and scalable production of complex multifunctional synthetic polymers. Here, we demonstrate that mucin glycoproteins, the gel-forming constituents of native mucus, are suitable for assembly into robust hydrogels capable of facilitating the sustained release of hydrophobic and hydrophilic drugs. Covalently-crosslinked mucin hydrogels were generated via exposure of methacrylated mucin to ultraviolet light in the presence of a free radical photoinitiator. The hydrogels exhibited an elastic modulus similar to that of soft mammalian tissue and were sensitive to proteolytic degradation by pronase. Paclitaxel, a hydrophobic anti-cancer drug, and polymyxin B, a positively-charged hydrophilic antibacterial drug, were retained in the hydrogels and released linearly with time over seven days. After four weeks of drug release, the hydrogels continued to release sufficient amounts of active paclitaxel to reduce HeLa cell viability and sufficient amounts of active polymyxin B to prevent bacterial proliferation. Along with previously-established anti-inflammatory, anti-viral, and hydrocarbon-solubilizing properties of mucin, the results of this study establish mucin as a readily-available, chemically-versatile, naturally-biocompatible alternative to complex multifunctional synthetic polymers as building blocks in the design of biomaterials for sustained drug delivery.
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Affiliation(s)
- Connor V Duffy
- Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Building 56-341C, Cambridge, MA 02139, USA
| | - Laurent David
- Ingénierie des Matériaux Polymères, Université de Lyon, Université Claude Bernard Lyon 1, UMR CNRS 5223, 15 Boulevard Latarjet, 69622 Villeurbanne Cedex, France
| | - Thomas Crouzier
- Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Building 56-341C, Cambridge, MA 02139, USA; Ingénierie des Matériaux Polymères, Université de Lyon, Université Claude Bernard Lyon 1, UMR CNRS 5223, 15 Boulevard Latarjet, 69622 Villeurbanne Cedex, France.
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39
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Powell JJ, Thomas-McKay E, Thoree V, Robertson J, Hewitt RE, Skepper JN, Brown A, Hernandez-Garrido JC, Midgley PA, Gomez-Morilla I, Grime GW, Kirkby KJ, Mabbott NA, Donaldson DS, Williams IR, Rios D, Girardin SE, Haas CT, Bruggraber SFA, Laman JD, Tanriver Y, Lombardi G, Lechler R, Thompson RPH, Pele LC. An endogenous nanomineral chaperones luminal antigen and peptidoglycan to intestinal immune cells. NATURE NANOTECHNOLOGY 2015; 10:361-9. [PMID: 25751305 PMCID: PMC4404757 DOI: 10.1038/nnano.2015.19] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/15/2014] [Accepted: 01/21/2015] [Indexed: 05/06/2023]
Abstract
In humans and other mammals it is known that calcium and phosphate ions are secreted from the distal small intestine into the lumen. However, why this secretion occurs is unclear. Here, we show that the process leads to the formation of amorphous magnesium-substituted calcium phosphate nanoparticles that trap soluble macromolecules, such as bacterial peptidoglycan and orally fed protein antigens, in the lumen and transport them to immune cells of the intestinal tissue. The macromolecule-containing nanoparticles utilize epithelial M cells to enter Peyer's patches, small areas of the intestine concentrated with particle-scavenging immune cells. In wild-type mice, intestinal immune cells containing these naturally formed nanoparticles expressed the immune tolerance-associated molecule 'programmed death-ligand 1', whereas in NOD1/2 double knockout mice, which cannot recognize peptidoglycan, programmed death-ligand 1 was undetected. Our results explain a role for constitutively formed calcium phosphate nanoparticles in the gut lumen and show how this helps to shape intestinal immune homeostasis.
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Affiliation(s)
- Jonathan J Powell
- Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK
| | - Emma Thomas-McKay
- Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK
| | - Vinay Thoree
- Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK
| | - Jack Robertson
- Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK
| | - Rachel E Hewitt
- Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK
| | - Jeremy N Skepper
- Cambridge Advanced Imaging Centre, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK
| | - Andy Brown
- Institute for Materials Research, SPEME, University of Leeds, Leeds LS2 9JT, UK
| | - Juan Carlos Hernandez-Garrido
- Departamento de Ciencia de los Materiales e Ingenieria Metalúrgica y Química Inorganica, Facultad de Ciencias, Universidad de Cádiz, Campus Universitario Rio San Pedro, Puerto Real (Cádiz) 11.510, Spain
| | - Paul A Midgley
- Department of Materials Science and Metallurgy, University of Cambridge, 27 Charles Babbage Road, Cambridge CB3 0FS, UK
| | - Inmaculada Gomez-Morilla
- Technische Universitaet Dresden, Fakultaet Maschinenwesen, Institut fuer Stroemungsmechanik, Dresden 01062, Germany
| | - Geoffrey W Grime
- Ion Beam Centre, Advanced Technology Institute, Faculty of Engineering and Physical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK
| | - Karen J Kirkby
- 1] Ion Beam Centre, Advanced Technology Institute, Faculty of Engineering and Physical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK [2] Institute of Cancer Sciences, The University of Manchester, 27 Palatine Road, Withington, Manchester M20 3LJ, UK
| | - Neil A Mabbott
- The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK
| | - David S Donaldson
- The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK
| | - Ifor R Williams
- Department of Pathology, Emory University School of Medicine, 615 Michael Street, Atlanta, Georgia 30322, USA
| | - Daniel Rios
- Department of Pathology, Emory University School of Medicine, 615 Michael Street, Atlanta, Georgia 30322, USA
| | - Stephen E Girardin
- Department of Laboratory Medicine and Pathobiology, 1 King's College Circle, Toronto M5S 1A8, Canada
| | - Carolin T Haas
- Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK
| | - Sylvaine F A Bruggraber
- Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK
| | - Jon D Laman
- 1] Department of Immunology, Erasmus MC, University Medical Centre and MS Centre ErasMS, PO Box 2040, Rotterdam 3000 CA, The Netherlands [2] Department of Neuroscience, Section Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Yakup Tanriver
- Department of Internal Medicine IV and Institute of Medical Microbiology and Hygiene, University Medical Center, Freiburg 79106, Germany
| | - Giovanna Lombardi
- Immunoregulation Laboratory, MRC Centre for Transplantation, King's College London, Guys' Hospital, London SE1 9RT, UK
| | - Robert Lechler
- Immunoregulation Laboratory, MRC Centre for Transplantation, King's College London, Guys' Hospital, London SE1 9RT, UK
| | - Richard P H Thompson
- 1] Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK [2] Royal College of Physicians, 11 St Andrews Place, Regent's Park, London NW1 4LE, UK
| | - Laetitia C Pele
- Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK
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Hinkley GK, Carpinone P, Munson JW, Powers KW, Roberts SM. Oral absorption of PEG-coated versus uncoated gold nanospheres: does agglomeration matter? Part Fibre Toxicol 2015; 12:9. [PMID: 25884802 PMCID: PMC4396175 DOI: 10.1186/s12989-015-0085-5] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2014] [Accepted: 03/04/2015] [Indexed: 11/17/2022] Open
Abstract
Background Particle size is thought to be a critical factor affecting the bioavailability of nanoparticles following oral exposure. Nearly all studies of nanoparticle bioavailability focus on characterization of the primary particle size of the material as supplied or as dosed, and not on agglomeration behavior within the gastrointestinal tract, which is presumably most relevant for absorption. Methods In the study reported here, snapshots of agglomeration behavior of gold nanospheres were evaluated in vivo throughout the gastrointestinal tract using transmission electron microscopy. Agglomeration state within the gastrointestinal tract was then used to help explain differences in gastrointestinal particle absorption, as indicated by tissue levels of gold detected using inductively coupled plasma mass spectrometry. Mice were dosed (10 mg/kg) with either 23 nm PEG-coated or uncoated gold nanospheres. Results Transmission electron microscopy demonstrates that PEG-coated gold nanoparticles can be observed as primary, un-agglomerated particles throughout the gastrointestinal tract and feces of dosed animals. In contrast, uncoated gold nanoparticles were observed to form agglomerates of several hundred nanometers in all tissues and feces. Inductively coupled plasma mass spectrometry shows significantly higher levels of gold in tissues from animals dosed with PEG-coated versus uncoated 23 nm gold nanoparticles. Retention of particles after a single oral gavage was also very high, with all tissues of animals dosed with PEG-coated particles having detectable levels of gold at 30 days following exposure. Conclusions Qualitative observation of these particles in vivo shows that dispersed PEG-coated particles are able to reach the absorptive tissues of the intestine while agglomerated uncoated particles are sequestered in the lumen of these tissues. However, the large differences observed for in vivo agglomeration behavior were not reflected in oral absorption, as indicated by gold tissue levels. Additional factors, such as surface chemistry, may have played a more important role than in vivo particle size and should be investigated further.
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Affiliation(s)
- Georgia K Hinkley
- Center for Environmental and Human Toxicology, University of Florida, Box 110885, Gainesville, FL, 32611, USA.
| | - Paul Carpinone
- Major Analytical and Particle Analysis Instrumentation Center, University of Florida, Box 116400, Gainesville, FL, 32611, USA.
| | - John W Munson
- Center for Environmental and Human Toxicology, University of Florida, Box 110885, Gainesville, FL, 32611, USA.
| | - Kevin W Powers
- Particle Engineering Research Center, University of Florida, Box 116135, Gainesville, FL, 32611, USA.
| | - Stephen M Roberts
- Center for Environmental and Human Toxicology, University of Florida, Box 110885, Gainesville, FL, 32611, USA.
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Walczak AP, Hendriksen PJM, Woutersen RA, van der Zande M, Undas AK, Helsdingen R, van den Berg HHJ, Rietjens IMCM, Bouwmeester H. Bioavailability and biodistribution of differently charged polystyrene nanoparticles upon oral exposure in rats. JOURNAL OF NANOPARTICLE RESEARCH : AN INTERDISCIPLINARY FORUM FOR NANOSCALE SCIENCE AND TECHNOLOGY 2015; 17:231. [PMID: 26028989 PMCID: PMC4440892 DOI: 10.1007/s11051-015-3029-y] [Citation(s) in RCA: 118] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2015] [Accepted: 05/04/2015] [Indexed: 05/22/2023]
Abstract
The likelihood of oral exposure to nanoparticles (NPs) is increasing, and it is necessary to evaluate the oral bioavailability of NPs. In vitro approaches could help reducing animal studies, but validation against in vivo studies is essential. Previously, we assessed the translocation of 50 nm polystyrene NPs of different charges (neutral, positive and negative) using a Caco-2/HT29-MTX in vitro intestinal translocation model. The NPs translocated in a surface charge-dependent manner. The present study aimed to validate this in vitro intestinal model by an in vivo study. For this, rats were orally exposed to a single dose of these polystyrene NPs and the uptake in organs was determined. A negatively charged NP was taken up more than other NPs, with the highest amounts in kidney (37.4 µg/g tissue), heart (52.8 µg/g tissue), stomach wall (98.3 µg/g tissue) and small intestinal wall (94.4 µg/g tissue). This partly confirms our in vitro findings, where the same NPs translocated to the highest extent. The estimated bioavailability of different types of NPs ranged from 0.2 to 1.7 % in vivo, which was much lower than in vitro (1.6-12.3 %). Therefore, the integrated in vitro model cannot be used for a direct prediction of the bioavailability of orally administered NPs. However, the model can be used for prioritizing NPs before further in vivo testing for risk assessment.
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Affiliation(s)
- Agata P. Walczak
- />Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen, The Netherlands
- />RIKILT Wageningen UR, P.O. Box 230, Akkermaalsbos 2, 6700 AE Wageningen, The Netherlands
| | - Peter J. M. Hendriksen
- />RIKILT Wageningen UR, P.O. Box 230, Akkermaalsbos 2, 6700 AE Wageningen, The Netherlands
| | - Ruud A. Woutersen
- />TNO Earth, Life and Social Sciences, Princetonlaan 6, 3584 CB Utrecht, The Netherlands
| | - Meike van der Zande
- />RIKILT Wageningen UR, P.O. Box 230, Akkermaalsbos 2, 6700 AE Wageningen, The Netherlands
| | - Anna K. Undas
- />RIKILT Wageningen UR, P.O. Box 230, Akkermaalsbos 2, 6700 AE Wageningen, The Netherlands
| | - Richard Helsdingen
- />RIKILT Wageningen UR, P.O. Box 230, Akkermaalsbos 2, 6700 AE Wageningen, The Netherlands
| | - Hans H. J. van den Berg
- />Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen, The Netherlands
| | - Ivonne M. C. M. Rietjens
- />Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen, The Netherlands
| | - Hans Bouwmeester
- />RIKILT Wageningen UR, P.O. Box 230, Akkermaalsbos 2, 6700 AE Wageningen, The Netherlands
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Yang H, Teng F, Wang P, Tian B, Lin X, Hu X, Zhang L, Zhang K, Zhang Y, Tang X. Investigation of a nanosuspension stabilized by Soluplus® to improve bioavailability. Int J Pharm 2014; 477:88-95. [DOI: 10.1016/j.ijpharm.2014.10.025] [Citation(s) in RCA: 70] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2014] [Revised: 08/28/2014] [Accepted: 10/10/2014] [Indexed: 11/26/2022]
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Odziomek M, Sosnowski TR, Gradoń L. The Influence of Functional Carrier Particles (FCPs) on the Molecular Transport Rate Through the Reconstructed Bronchial Mucus: In Vitro Studies. Transp Porous Media 2014. [DOI: 10.1007/s11242-014-0409-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Walczak AP, Kramer E, Hendriksen PJM, Tromp P, Helsper JPFG, van der Zande M, Rietjens IMCM, Bouwmeester H. Translocation of differently sized and charged polystyrene nanoparticles in in vitro intestinal cell models of increasing complexity. Nanotoxicology 2014; 9:453-61. [DOI: 10.3109/17435390.2014.944599] [Citation(s) in RCA: 130] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Agata P. Walczak
- Division of Toxicology, Wageningen University, Wageningen, The Netherlands,
- RIKILT Wageningen UR, Wageningen, The Netherlands, and
| | | | | | - Peter Tromp
- TNO Earth, Life and Social Sciences, Utrecht, The Netherlands
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Groo AC, Lagarce F. Mucus models to evaluate nanomedicines for diffusion. Drug Discov Today 2014; 19:1097-108. [DOI: 10.1016/j.drudis.2014.01.011] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2013] [Revised: 12/20/2013] [Accepted: 01/24/2014] [Indexed: 01/25/2023]
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M-M P, Somchue W, Shiowatana J, Siripinyanond A. Flow field-flow fractionation for particle size characterization of selenium nanoparticles incubated in gastrointestinal conditions. Food Res Int 2014. [DOI: 10.1016/j.foodres.2014.01.040] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Groo AC, Mircheva K, Bejaud J, Ailhas C, Panaiotov I, Saulnier P, Ivanova T, Lagarce F. Development of 2D and 3D Mucus Models and Their Interactions with Mucus-Penetrating Paclitaxel-Loaded Lipid Nanocapsules. Pharm Res 2014; 31:1753-65. [DOI: 10.1007/s11095-013-1280-4] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2013] [Accepted: 12/11/2013] [Indexed: 01/26/2023]
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Ma Y, Coombes AGA. Designing colon-specific delivery systems for anticancer drug-loaded nanoparticles: An evaluation of alginate carriers. J Biomed Mater Res A 2013; 102:3167-76. [DOI: 10.1002/jbm.a.34988] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2013] [Revised: 09/23/2013] [Accepted: 10/02/2013] [Indexed: 01/30/2023]
Affiliation(s)
- Yiming Ma
- Pharmacy Australia Centre of Excellence; The University of Queensland; Woolloongabba Queensland 4102 Australia
| | - Allan G. A. Coombes
- Pharmacy Australia Centre of Excellence; The University of Queensland; Woolloongabba Queensland 4102 Australia
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Jain V, Jain B, Tiwari P, Saini J, Jain UK, Pandey RS, Kumar M, Katare OP, Chandra R, Madan J. Nanosolvated microtubule-modulating chemotherapeutics: a case-to-case study. Anticancer Drugs 2013; 24:327-36. [PMID: 23411683 DOI: 10.1097/cad.0b013e32835ec414] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
About 10% of the drugs in the preclinical stage are poorly soluble, 40% of the drugs in the pipeline have poor solubility, and even 60% of drugs coming directly from synthesis have aqueous solubility below 0.1 mg/ml. Out of the research around, 40% of lipophilic drug candidates fail to reach the market despite having potential pharmacodynamic activities. Microtubule-modulating chemotherapeutics is an important class of cancer chemotherapy. Most chemotherapeutics that belong to this category are plant-derived active constituents, such as vincristine, vinblastine, colchicine, docetaxel, paclitaxel, and noscapinoids. The pKa of a drug considerably affects its solubility in physiological fluids and consequently bioavailability. It usually ranges from 5 to 12 for microtubule-modulating drugs. Hence, the solubility of these drugs in physiological fluids is considerably affected by a change in pH. However, because of unpredictable parameters involved in poor solubility and the low oral bioavailability of these chemotherapeutics during the early phases of drug development, they often have an unusual pharmacokinetic profile. This makes the development process of novel chemotherapeutics slow, inefficient, patient-unfriendly, and very costly, emphasizing a need for more rational approaches on the basis of preclinical concepts. Nanosolvation is a process of increasing the polarity of a hydrophobic molecule either by solvation or cavitization in a hydrophilic macrocycle. The present review therefore focuses on the techniques applied in nanosolvation of microtubule-modulating chemotherapeutics to enhance solubility and bioavailability. The methodologies described will be highly beneficial for anticancer researchers to follow a trend of rational drug development.
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Affiliation(s)
- Vibhor Jain
- Department of Pharmaceutics, School of Pharmacy, Chouksey Engineering College, Bilaspur, India
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Ensign LM, Cone R, Hanes J. Oral drug delivery with polymeric nanoparticles: the gastrointestinal mucus barriers. Adv Drug Deliv Rev 2012; 64:557-70. [PMID: 22212900 DOI: 10.1016/j.addr.2011.12.009] [Citation(s) in RCA: 1037] [Impact Index Per Article: 79.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2011] [Revised: 12/02/2011] [Accepted: 12/14/2011] [Indexed: 12/14/2022]
Abstract
Oral delivery is the most common method for drug administration. However, poor solubility, stability, and bioavailability of many drugs make achieving therapeutic levels via the gastrointestinal (GI) tract challenging. Drug delivery must overcome numerous hurdles, including the acidic gastric environment and the continuous secretion of mucus that protects the GI tract. Nanoparticle drug carriers that can shield drugs from degradation and deliver them to intended sites within the GI tract may enable more efficient and sustained drug delivery. However, the rapid secretion and shedding of GI tract mucus can significantly limit the effectiveness of nanoparticle drug delivery systems. Many types of nanoparticles are efficiently trapped in and rapidly removed by mucus, making controlled release in the GI tract difficult. This review addresses the protective barrier properties of mucus secretions, how mucus affects the fate of orally administered nanoparticles, and recent developments in nanoparticles engineered to penetrate the mucus barrier.
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Affiliation(s)
- Laura M Ensign
- Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
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