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Chen L, Zhang S, Duan Y, Song X, Chang M, Feng W, Chen Y. Silicon-containing nanomedicine and biomaterials: materials chemistry, multi-dimensional design, and biomedical application. Chem Soc Rev 2024; 53:1167-1315. [PMID: 38168612 DOI: 10.1039/d1cs01022k] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2024]
Abstract
The invention of silica-based bioactive glass in the late 1960s has sparked significant interest in exploring a wide range of silicon-containing biomaterials from the macroscale to the nanoscale. Over the past few decades, these biomaterials have been extensively explored for their potential in diverse biomedical applications, considering their remarkable bioactivity, excellent biocompatibility, facile surface functionalization, controllable synthesis, etc. However, to expedite the clinical translation and the unexpected utilization of silicon-composed nanomedicine and biomaterials, it is highly desirable to achieve a thorough comprehension of their characteristics and biological effects from an overall perspective. In this review, we provide a comprehensive discussion on the state-of-the-art progress of silicon-composed biomaterials, including their classification, characteristics, fabrication methods, and versatile biomedical applications. Additionally, we highlight the multi-dimensional design of both pure and hybrid silicon-composed nanomedicine and biomaterials and their intrinsic biological effects and interactions with biological systems. Their extensive biomedical applications span from drug delivery and bioimaging to therapeutic interventions and regenerative medicine, showcasing the significance of their rational design and fabrication to meet specific requirements and optimize their theranostic performance. Additionally, we offer insights into the future prospects and potential challenges regarding silicon-composed nanomedicine and biomaterials. By shedding light on these exciting research advances, we aspire to foster further progress in the biomedical field and drive the development of innovative silicon-composed nanomedicine and biomaterials with transformative applications in biomedicine.
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Affiliation(s)
- Liang Chen
- Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, P. R. China.
| | - Shanshan Zhang
- Department of Ultrasound Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P. R. China
| | - Yanqiu Duan
- Laboratory Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, P. R. China.
| | - Xinran Song
- Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, P. R. China.
| | - Meiqi Chang
- Laboratory Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, P. R. China.
| | - Wei Feng
- Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, P. R. China.
| | - Yu Chen
- Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, P. R. China.
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Xia Y, Gu M, Wang J, Zhang X, Shen T, Shi X, Yuan WE. Tumor microenvironment-activated, immunomodulatory nanosheets loaded with copper(II) and 5-FU for synergistic chemodynamic therapy and chemotherapy. J Colloid Interface Sci 2024; 653:137-147. [PMID: 37713912 DOI: 10.1016/j.jcis.2023.09.042] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 08/18/2023] [Accepted: 09/08/2023] [Indexed: 09/17/2023]
Abstract
The tumor microenvironment (TME) has a redox state that differs greatly from normal tissues, as characterized by the overexpression of H2O2 and glutathione (GSH). To address the GSH-related restrictions on chemodynamic therapy (CDT) efficacy, we have developed a Cu(II)-based CDT strategy. In this study, a novel organic-inorganic hybrid drug delivery system (LDH/HA/5-FU) was conceived and prepared by the intercalation of 5-FU into the interlayer of copper-aluminum layered double hydroxide (CuAl-LDH) via ion exchange strategy and the adsorption of hyaluronic acid (HA) on the surface of CuAl-LDH. Taking advantage of the pH-degradable property of CuAl-LDH and the CD44-targeting property of HA, the formed LDH/HA/5-FU nanosheets could specifically target tumor cells' overexpressing CD44 receptor, rapidly release Cu(II) and 5-FU in tumor cells, inducing tumor cell apoptosis and cuproptosis, and long-term intracellular GSH depletion and toxic hydroxyl radicals (·OH) generation could be achieved through the cyclic catalytic reaction of Cu(I)/Cu(II). Meanwhile, peritumoral injection of LDH/HA/5-FU nanosheets might function as an adjuvant to increase the levels of antitumor tumor-associated macrophages (TAMs) and T cells. In vivo experiments further verified that the intelligently designed LDH/HA/5-FU nanosheets successfully promoted the immune systems, with an excellent inhibition efficacy towards tumors by combining Cu-based CDT and chemotherapy, showing promising potential for solid tumor treatments.
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Affiliation(s)
- Yi Xia
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, China; Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China; National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Muge Gu
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, China; Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China; National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Jiayu Wang
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, China; Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China; National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Xiangqi Zhang
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, China; Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China; National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Tianyi Shen
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, China; Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China; National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Xiaoying Shi
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, China; Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China; National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Wei-En Yuan
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, China; Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China; National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 200240, China.
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Ghasemizadeh H, Pourmadadi M, Yazdian F, Rashedi H, Navaei-Nigjeh M, Rahdar A, Díez-Pascual AM. Novel carboxymethyl cellulose-halloysite-polyethylene glycol nanocomposite for improved 5-FU delivery. Int J Biol Macromol 2023; 232:123437. [PMID: 36708898 DOI: 10.1016/j.ijbiomac.2023.123437] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 01/15/2023] [Accepted: 01/22/2023] [Indexed: 01/27/2023]
Abstract
Drug nano-carriers are crucial for achieving targeted treatment against cancer disorders with minimal side effects. In this study, a pH-responsive nanocomposite based on halloysite nanotube (HNT) coated with carboxymethyl cellulose (CMC)/polyethylene glycol (PEG) hydrogel for controlled delivery of 5-Fluorouracil (5-FU), a hydrophobic chemotherapy drug prescribed for different types of cancers was synthesized for the first time using the water-in-oil-in-water (W/O/W) technique. The developed CMC/PEG/HNT/5-FU nanocomposite was characterized by dynamic light scattering (DLS), zeta potential, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and Field emission scanning electron microscope (FE-SEM) to get information about the particle size, surface charge, interactions between functional groups, crystalline structure and morphology, respectively. High efficiencies in terms of drug entrapment and loading (46 % and 87 %, respectively) were attained. In-vitro drug release results revealed an improved and sustained 5-FU delivery in an acid environment compared to the physiological medium, corroborating the pH-sensitivity of the developed nano-carrier. Flow cytometry and MTT assays demonstrated that the 5-FU loaded nanocomposite had considerable cytotoxicity on MCF-7 breast cancer cells while it is not toxic against L929 fibroblast cells. The nanocomposite synthesized herein could serve as a platform for the pH-sensitive release of anti-cancer drugs.
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Affiliation(s)
- Haniyeh Ghasemizadeh
- Department of Biotechnology, School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran
| | - Mehrab Pourmadadi
- Department of Biotechnology, School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran
| | - Fatemeh Yazdian
- Department of Life Science Engineering, Faculty of New Science and Technologies, University of Tehran, Tehran, Iran.
| | - Hamid Rashedi
- Department of Biotechnology, School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran.
| | - Mona Navaei-Nigjeh
- Pharmaceutical Sciences Research Center, the Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Abbas Rahdar
- Department of Physics, Faculty of Sciences, University of Zabol, Zabol 538-98615, Iran.
| | - Ana M Díez-Pascual
- Universidad de Alcalá, Facultad de Ciencias, Departamento de Química Analítica, Química Física e Ingeniería Química, Ctra. Madrid-Barcelona Km. 33.6, 28805 Alcalá de Henares, Madrid, Spain.
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Tipa C, Cidade MT, Borges JP, Costa LC, Silva JC, Soares PIP. Clay-Based Nanocomposite Hydrogels for Biomedical Applications: A Review. NANOMATERIALS (BASEL, SWITZERLAND) 2022; 12:3308. [PMID: 36234440 PMCID: PMC9565291 DOI: 10.3390/nano12193308] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 09/14/2022] [Accepted: 09/15/2022] [Indexed: 06/16/2023]
Abstract
In recent decades, new and improved materials have been developed with a significant interest in three-dimensional (3D) scaffolds that can cope with the diverse needs of the expanding biomedical field and promote the required biological response in multiple applications. Due to their biocompatibility, ability to encapsulate and deliver drugs, and capacity to mimic the extracellular matrix (ECM), typical hydrogels have been extensively investigated in the biomedical and biotechnological fields. The major limitations of hydrogels include poor mechanical integrity and limited cell interaction, restricting their broad applicability. To overcome these limitations, an emerging approach, aimed at the generation of hybrid materials with synergistic effects, is focused on incorporating nanoparticles (NPs) within polymeric gels to achieve nanocomposites with tailored functionality and improved properties. This review focuses on the unique contributions of clay nanoparticles, regarding the recent developments of clay-based nanocomposite hydrogels, with an emphasis on biomedical applications.
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Affiliation(s)
- Cezar Tipa
- CENIMAT|i3N, Department of Materials Science, School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal
| | - Maria T. Cidade
- CENIMAT|i3N, Department of Materials Science, School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal
| | - João P. Borges
- CENIMAT|i3N, Department of Materials Science, School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal
| | - Luis C. Costa
- I3N and Physics Department, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Jorge C. Silva
- CENIMAT|i3N, Department of Physics, School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal
| | - Paula I. P. Soares
- CENIMAT|i3N, Department of Materials Science, School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal
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Farshi Azhar F, Rezaei M, Olad A, Mousazadeh H. The effect of montmorillonite in graphene oxide/chitosan nanocomposite on controlled release of gemcitabine. Polym Bull (Berl) 2022. [DOI: 10.1007/s00289-021-03774-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Faid AH, Shouman SA, Thabet NA, Badr YA, Sliem MA. Laser Enhanced Combinatorial Chemo-photothermal Therapy of Green Synthesis Gold Nanoparticles Loaded with 6Mercaptopurine on Breast Cancer Model. J Pharm Innov 2022. [DOI: 10.1007/s12247-022-09626-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Abstract
Purpose
We tend to evaluated a method for loading 6Mercaptopurine (6MP) on green synthesized hybrid chitosan gold nanoparticles (AuNPs) forming 6MP-AuNPs nanocomposite for the first time in combinatorial chemo-photothermal therapy.
Methods
The AuNPs were synthesized using chitosan as a reducing and capping agent. Different concentrations of 6MP were mixed AuNPs. Cells were incubated with 6MP and 6MP loaded AuNPs for 48 h and then exposed to laser.
Results
AuNPs and 6MP-AuNPs nanocomposite have small sizes of 18 ± 4 and 25 ± 5 nm and exhibit high stability with Zeta potential of 55.9 ± 6.3 and 57 ± 4 mV. 6MP-AuNPs nanocomposite irradiated with Diode Pumped Solid State (DPSS) laser showed a maximum inhibition in cell viability reaching 63% at 1.25 µM.
Conclusions
A hybrid chitosan gold nanoparticle is a powerful anti-cancer drug carrier as well as photothermal agent in combinatorial chemo-photothermal therapy.
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Assessment of the genotoxic potential of three novel composite nanomaterials using human lymphocytes and the fruit fly Drosophila melanogaster as model systems. CHEMICAL ENGINEERING JOURNAL ADVANCES 2022. [DOI: 10.1016/j.ceja.2021.100230] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
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Pourmanouchehri Z, Ebrahimi S, Limoee M, Jalilian F, Janfaza S, Vosoughi A, Behbood L. Controlled release of 5-fluorouracil to melanoma cells using a hydrogel/micelle composites based on deoxycholic acid and carboxymethyl chitosan. Int J Biol Macromol 2022; 206:159-166. [PMID: 35218806 DOI: 10.1016/j.ijbiomac.2022.02.096] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 01/28/2022] [Accepted: 02/16/2022] [Indexed: 12/31/2022]
Abstract
5-Fluorouracil (5-FU) is an antimetabolite drug widely used for the treatment of skin cancer. Despite its proven efficacy in treating malignancies, its systemic administration is limited due to severe side effects. To address this issue, topical delivery of 5-FU has been proposed as an alternative approach for the treatment of skin cancer, however, the poor permeability of 5-FU through the skin is still a challenge. Here, we introduced a pH-responsive micellar hydrogel system based on deoxycholic acid micelle (DCA Mic) and carboxymethyl chitosan hydrogel (CMC Hyd) to enhance 5-FU efficacy against skin cancer and reduce its systemic side effects by improving its delivery into the skin. The properties of the Mic/Hyd system were determined by Fourier-transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), zeta sizer, atomic force microscopy (AFM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Drug release studies showed pH-dependent properties of the Hyd. The final formulation was demonstrated to have enhanced anticancer activity than 5-FU against the growth of melanoma cells. The 5-FU@Mic-Hyd could be a promising delivery platform with enhanced efficacy in the management of skin cancer without systemic toxicity.
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Affiliation(s)
- Zahra Pourmanouchehri
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Sayeh Ebrahimi
- Student Research Committee, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mazdak Limoee
- Nano Drug Delivery Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Fereshteh Jalilian
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Sajad Janfaza
- School of Engineering, University of British Columbia, Kelowna, BC, Canada; Departments of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada
| | - Amirhossein Vosoughi
- Student Research Committee, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Leila Behbood
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; Nano Drug Delivery Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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Karataş D, Bahadori F, Tekin A, Ergin Kizilcay G, Celik MS. Enhancing the Kinetic Stability of Polymeric Nanomicelles (PLGA) Using Nano-Montmorillonite for Effective Targeting of Cancer Tumors. J Phys Chem B 2022; 126:463-479. [PMID: 35005971 DOI: 10.1021/acs.jpcb.1c07334] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
The toxic profile of chemical cross-linkers used in enhancing the stability of self-assembled nanomicelles made of amphiphilic polymeric materials hinders their use in clinical applications. This study was aimed to use the layered structure of Na-montmorillonite (MMT) as a stabilizer for nanomicelles made of poly(d,l-lactide-co-glycolide) (PLGA) amphiphilic polymer. The size of Na-MMT was reduced below 40 nm (nano-MMT) by processing in an attritor prior to its incorporation with PLGA. Hybrid PLGA nano-MMT (PM) nanoparticles (NPs) were prepared using dialysis nanoprecipitation. The size distribution was measured using dynamic light scattering (DLS). Loading 1250 μg of the model drug molecule curcumin to PM (PMC) resulted in obtaining 88 nm-sized particles, suitable for passive targeting of cancer tumors. The structure of nano-MMT and its position in PMC were investigated using FT-IR, differential scanning chalorimetry (DSC), XRF, XRD, ESEM, and EDAX assays, all of which showed the exfoliated structure of nano-MMT incorporated with both hydrophilic and hydrophobic blocks of PLGA. Curcumin was mutually loaded to PLGA and nano-MMT. This firm incorporation caused a serious extension in the release of curcumin from PMC compared to PLGA (PC). Fitting the release profile to different mathematical models showed the remarkable role of nano-MMT in surface modification of PLGA NPs. The ex vivo dynamic model showed the enhanced stability of PMC in simulated blood flow, while cytotoxicity assays showed that nano-MMT does not aggravate the good toxic profile of PLGA but improves the anticancer effect of payload. Nano-MMT could be used as an effective nontoxic stabilizer agent for self-assembled NPs.
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Affiliation(s)
- Deniz Karataş
- Mineral Processing Engineering Department, Istanbul Technical University, 34469 Maslak, Turkey
| | - Fatemeh Bahadori
- Faculty of Pharmacy, Department of Pharmaceutical Biotechnology, Bezmialem Vakif University, 34093 Fatih, Turkey
| | - Adem Tekin
- Informatics Institute, Istanbul Technical University, 34469 Maslak, Turkey
| | - Gamze Ergin Kizilcay
- Department of Analytical Chemistry, Faculty of Pharmacy, Istanbul University, 34116 Beyazit, Istanbul, Turkey
| | - Mehmet Sabri Celik
- Mineral Processing Engineering Department, Istanbul Technical University, 34469 Maslak, Turkey
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Randive DS, Gavade AS, Shejawal KP, Bhutkar MA, Bhinge SD, Jadhav NR. Colon targeted dosage form of Capecitabine using folic acid anchored modified carbon nanotube: in vitro cytotoxicity, apoptosis and in vivo roentgenographic study. Drug Dev Ind Pharm 2021; 47:1401-1412. [PMID: 34663149 DOI: 10.1080/03639045.2021.1994988] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVE Development of dosage form comprising of Capecitabine loaded carbon nanotubes for its targeted delivery to the colon. METHOD Single walled carbon nanotubes (SWCNT) were functionalized by -COOH and Chitosan along with Folic acid. Capecitabine was loaded in these SWCNT's, and the system was analyzed by FTIR, SEM and Raman spectroscopy. Percent drug loading was assessed and the cytotoxicity (COLO320DM and HT29) was verified by using MTT and SRB assay. The apoptosis study was carried out by flowcytometry. The system was enclosed in an enteric coated capsule with pH sensitive polymers and characterized for invitro disintegration, dissolution and invivo roentgenographic studies. RESULTS FTIR, Raman and XRD studies indicated the confirmation of attachments, whereas SEM exhibited size range of 200-500 nm. Drug loading capacity was observed to be 94.63 ± 1.07%. Cytotoxicity studies of Capecitabine and FA-CHI-F-SWCNT-Capecitabine against COLO320DM by using MTT assay showed that FA-CHI-F-SWCNT- Capecitabine exhibited 86.45 ± 0.5788% inhibition whereas pure Capecitabine showed 50.52 ± 0.3106% inhibition. Against HT29, the % inhibition was observed to be 82.76 ± 0.4668% and 56.41 ± 0.2316% respectively for FA-CHI-F-SWCNT-Capecitabine and pure Capecitabine. In case of SRB assay of COLO320DM, the FA-CHI-F-SWCNT-Capecitabine exhibited 89.62 ± 0.4095% inhibition and Capecitabine showed 84.36 ± 0.2559% inhibition, whereas against HT29, FA-CHI-F-SWCNT-Capecitabine showed 81.36 ± 0.2958% inhibition and Capecitabine exhibited 90.62 ± 0.4196% inhibition. CONCLUSION FA-CHI-F-SWCNT loaded system revealed better cytotoxicity as compared with pure Capecitabine against two different cell lines. Invivo studies revealed that the prepared capsule formulation remained intact in the stomach thereby preventing drug release in the gastric milieu.
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Affiliation(s)
- Dheeraj S Randive
- Pharmaceutics Department Rajarambapu College of Pharmacy, Sangli, Maharashtra, India
| | - Akshata S Gavade
- Pharmaceutics Department Rajarambapu College of Pharmacy, Sangli, Maharashtra, India
| | - Kiran P Shejawal
- Pharmaceutics Department Rajarambapu College of Pharmacy, Sangli, Maharashtra, India
| | - Mangesh A Bhutkar
- Pharmaceutics Department Rajarambapu College of Pharmacy, Sangli, Maharashtra, India
| | - Somnath D Bhinge
- Chemistry Department Rajarambapu College of Pharmacy, Sangli, Maharashtra, India
| | - Namdeo R Jadhav
- Pharmaceutics Department Bharati vidyapeeth College of Pharmacy, Kolhapur, Maharashtra, India
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Optimization delivery of 5-fluorouracil onto different morphologies of ZnO NPs: release and functional effects against colorectal cancer cell lines. CHEMICAL PAPERS 2021. [DOI: 10.1007/s11696-021-01625-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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12
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Obireddy SR, Subbarao SMC, Venkata KRKS, Lai W. Development and Characterization of Montmorillonite‐Based Hybrid Materials for pH‐Responsive Drug Delivery. ChemistrySelect 2021. [DOI: 10.1002/slct.202004711] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Affiliation(s)
| | | | | | - Wing‐Fu Lai
- School of Life and Health Sciences The Chinese University of Hong Kong (Shenzhen) Shenzhen China Department of Applied Biology and Chemical Technology Hong Kong Polytechnic University, Hong Kong Special Administrative Region China
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13
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Tan D, Li Y, Zhang Z, Sun S, Sun H, Li B. Selective Loading and Prolonged Release of 5-Fluorouracil in the Nanoconfined Interlayer Space of Montmorillonite. JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY 2021; 21:781-787. [PMID: 33213679 DOI: 10.1166/jnn.2021.18730] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Montmorillonite was used as a carrier for the anticancer drug 5-fluorouracil (5FU). The selective loading of 5FU into the nanoconfined interlayer space of montmorillonite was achieved by rinsing off the weakly bonded 5FU from the external surface. The 5FU loading content in montmorillonite was 3.2 mass%. The intercalated 5FU was in an amorphous state and might be arranged as a roughly vertical monolayer in the interlayer space of montmorillonite. The intercalated 5FU showed a high thermal stability due to the protection of the montmorillonite layers. The release profiles of the intercalated 5FU were well fitted with the modified Korsmeyer-Peppas model. The montmorillonite exhibited a prolonged release of 5FU due to the restriction of the outward diffusion of intercalated 5FU. The 5FU/montmorillonite system has promising potential for oral administration for colonspecific delivery.
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Affiliation(s)
- Daoyong Tan
- Key Laboratory of Solid Waste Treatment and Resource Recycle, Ministry of Education, School of Environment and Resource, Southwest University of Science and Technology, Sichuan Engineering Lab of Non-Metallic Mineral Powder Modification & High-Value Utilization, Mianyang 621010, China
| | - Yan Li
- Key Laboratory of Solid Waste Treatment and Resource Recycle, Ministry of Education, School of Environment and Resource, Southwest University of Science and Technology, Sichuan Engineering Lab of Non-Metallic Mineral Powder Modification & High-Value Utilization, Mianyang 621010, China
| | - Zheng Zhang
- Key Laboratory of Solid Waste Treatment and Resource Recycle, Ministry of Education, School of Environment and Resource, Southwest University of Science and Technology, Sichuan Engineering Lab of Non-Metallic Mineral Powder Modification & High-Value Utilization, Mianyang 621010, China
| | - Shiyong Sun
- Key Laboratory of Solid Waste Treatment and Resource Recycle, Ministry of Education, School of Environment and Resource, Southwest University of Science and Technology, Sichuan Engineering Lab of Non-Metallic Mineral Powder Modification & High-Value Utilization, Mianyang 621010, China
| | - Hongjuan Sun
- Key Laboratory of Solid Waste Treatment and Resource Recycle, Ministry of Education, School of Environment and Resource, Southwest University of Science and Technology, Sichuan Engineering Lab of Non-Metallic Mineral Powder Modification & High-Value Utilization, Mianyang 621010, China
| | - Bowen Li
- Department of Materials Science and Engineering, Michigan Technological University, Houghton, MI, 49931, USA
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Dong J, Cheng Z, Tan S, Zhu Q. Clay nanoparticles as pharmaceutical carriers in drug delivery systems. Expert Opin Drug Deliv 2020; 18:695-714. [PMID: 33301349 DOI: 10.1080/17425247.2021.1862792] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Clay minerals are a class of silicates with chemical inertness, colloid, and thixotropy, which have excellent physicochemical properties, good biocompatibility, low toxicity, and have high application potential in biomedical fields. These inorganic materials have been widely used in pharmaceutical excipients and active substances. In recent years, nanoclay mineral materials have been used as drug vehicles for the delivery of a variety of drugs based on their broad specific surface area, rich porosity, diverse morphology, good adsorption performance, and high ion exchange capacity. AREAS COVERED This review introduces the structures, properties, and applications of various common natural and synthetic nanoclay materials as drug carriers. Natural nanoclays have different morphologies including nanoplates, nanotubes, and nanofibers. Synthetic materials have controllable sizes and flexible structures, where mesoporous silica nanoparticles, laponite, and imogolite are typical ones. These inorganic nanoparticles are often linked to polymers to form multifunctional drug delivery systems for better pharmaceutical performance. EXPERT OPINION The clay nanomaterials have typical properties, including enhanced solubility of insoluble drugs, targeting therapeutic sites, controlled release, and stimulation of responsive drug delivery systems.
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Affiliation(s)
- Jiani Dong
- Department of Pharmacy, Xiangya School of Pharmaceutical Sciences in Central South University, Changsha, Hunan, China
| | - Zeneng Cheng
- Department of Pharmacy, Xiangya School of Pharmaceutical Sciences in Central South University, Changsha, Hunan, China
| | - Songwen Tan
- Department of Pharmacy, Xiangya School of Pharmaceutical Sciences in Central South University, Changsha, Hunan, China
| | - Qubo Zhu
- Department of Pharmacy, Xiangya School of Pharmaceutical Sciences in Central South University, Changsha, Hunan, China
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15
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Anticancer activity of lanthanum (III) and europium (III) 5‐fluorouracil complexes on Caco‐2 cell line. Appl Organomet Chem 2020. [DOI: 10.1002/aoc.5594] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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16
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Abukhadra MR, Refay NM, El-Sherbeeny AM, El-Meligy MA. Insight into the Loading and Release Properties of MCM-48/Biopolymer Composites as Carriers for 5-Fluorouracil: Equilibrium Modeling and Pharmacokinetic Studies. ACS OMEGA 2020; 5:11745-11755. [PMID: 32478266 PMCID: PMC7254798 DOI: 10.1021/acsomega.0c01078] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Accepted: 05/05/2020] [Indexed: 05/03/2023]
Abstract
The effect of the integration between MCM-48 and some biopolymers (starch, chitosan, and β-cyclodextrin) on enhancing the pharmaceutical properties of MCM-48 as advanced carriers for the 5-fluorouracil drug was studied considering the loading capacities and the release profiles. The prepared carriers are MCM-48/chitosan (MCM/CH), MCM-48/starch composite (MCM/ST), and MCM-48/β-Cyclodextrin (MCM/CD). They emphasized excellent 5-Fu loading capacities of 141.2 mg/g (MCM-48), 156.6 mg/g (MCM/ST), 191 mg/g (MCM/CH), and 170 mg/g (MCM/CD), reflecting significant enhancement in the loading capacities. The kinetic and equilibrium investigation suggested physisorption loading of 5-Fu drug in a monolayer form for MCM-48, MCM/ST, and MCM/CH (Langmuir) and in a multilayer form for MCM/CD (Freundlich). This was supported by the estimated adsorption energies (0.23 kJ/mol (MCM-48), 0.26 kJ/mol (MCM/ST), 0.3 kJ/mol (MCM/CH), and 0.75 kJ/mol (MCM/CD)) and the thermodynamic parameters of free energy and enthalpy. The obtained release profiles for 80 h reflected significant controlling for the releasing behavior of MCM/48 on integrating its structure by adjusting the type of the selected polymer and its ratio. The pharmacokinetic modeling and the diffusion exponent from the Korsmeyer-Peppas model suggested non-Fickian transport behavior (a combination of erosion and diffusion releasing mechanism) for MCM/ST, MCM/CH, and MCM/CD and Fickian diffusion behavior (diffusion releasing mechanism) for MCM-48.
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Affiliation(s)
- Mostafa R. Abukhadra
- Geology
Department, Faculty of Science, Beni-Suef
University, Beni-Suef
City 62511, Egypt
- Materials
Technologies and their Applications Lab, Geology Department, Faculty
of Science, Beni-Suef University, Beni-Suef City 62511, Egypt
| | - Nermen M. Refay
- Materials
Technologies and their Applications Lab, Geology Department, Faculty
of Science, Beni-Suef University, Beni-Suef City 62511, Egypt
- Chemistry
Department, Faculty of Science, Beni-Suef
University, Beni-Suef City 62511, Egypt
| | - Ahmed M. El-Sherbeeny
- Industrial
Engineering Department, College of Engineering, King Saud University, P.O. Box 800, Riyadh 11421, Saudi Arabia
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Belmessaoud NB, Bouslah N, Haddadine N. Clay/(PEG-CMC) biocomposites as a novel delivery system for ibuprofen. JOURNAL OF POLYMER ENGINEERING 2020. [DOI: 10.1515/polyeng-2019-0390] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
AbstractIn this study we report on the preparation and characterization of biocomposites based on a sodium montmorillonite-ibuprofen (MtIb) hybrid and neat poly(ethylene glycol), neat sodium carboxymethylcellulose or poly(ethylene glycol)-carboxymethylcellulose blend 50/50 biocomposites as drug carriers. Ib, a poorly soluble drug, was first intercalated into sodium Mt and then the resulting hybrid was compounded with the different polymeric matrices. Ib incorporation efficiency in Mt was determined by UV-visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction and thermal analysis. Both X-ray diffraction and differential scanning calorimetric studies revealed that the intercalation of Ib between the clay layers induced amorphization of the drug. Differential scanning calorimetry and Fourier transform infrared spectroscopy revealed the development of strong interactions between Ib and the polymer matrix. A study of the release of Ib from the synthesized biocomposites in simulated intestinal fluid (pH 7.4) was investigated. To better understand the release mechanism of drug molecules from the different carriers, several kinetic models have been applied.
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Affiliation(s)
- Nesma Baa Belmessaoud
- USTHB, Laboratoire de Synthèse Macromoléculaire et Thioorganique Macromoléculaire (LSMTM), Faculté de Chimie, Université des Sciences et de la Technologie Houari Boumediene, El Alia, BP 32, Bab Ezzouar, 16111, Algiers, Algeria
| | - Naima Bouslah
- USTHB, Laboratoire de Synthèse Macromoléculaire et Thioorganique Macromoléculaire (LSMTM), Faculté de Chimie, Université des Sciences et de la Technologie Houari Boumediene, El Alia, BP 32, Bab Ezzouar, 16111, Algiers, Algeria
| | - Nabila Haddadine
- USTHB, Laboratoire de Synthèse Macromoléculaire et Thioorganique Macromoléculaire (LSMTM), Faculté de Chimie, Université des Sciences et de la Technologie Houari Boumediene, El Alia, BP 32, Bab Ezzouar, 16111, Algiers, Algeria
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18
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Development of an oral bentonite-based modified-release freeze-dried powder of vactosertib: Pharmacokinetics and anti-colitis activity in rodent models of ulcerative colitis. Int J Pharm 2020; 578:119103. [DOI: 10.1016/j.ijpharm.2020.119103] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Revised: 01/10/2020] [Accepted: 01/30/2020] [Indexed: 12/13/2022]
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19
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Xiao X, Liang S, Zhao Y, Huang D, Xing B, Cheng Z, Lin J. Core-shell structured 5-FU@ZIF-90@ZnO as a biodegradable nanoplatform for synergistic cancer therapy. NANOSCALE 2020; 12:3846-3854. [PMID: 31995084 DOI: 10.1039/c9nr09869k] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
High treatment efficiency and low drug toxicity are two key factors in tumor therapy. The development of multifunctional drug carrier systems is of great significance for the diagnosis and therapy of tumors. Herein, a novel biodegradable treatment system based on zeolitic imidazolate framework-90 (ZIF-90) was designed in this study. This 5-FU@ZIF-90@ZnO (FZZ) drug delivery system achieves synergistic treatment with antineoplastic 5-fluorouracil (5-FU) and zinc oxide, and also has good dispersibility in the acidic tumor microenvironment (TME), which enables the drug to achieve pH-controlled delivery in acidic organisms. Interestingly, zinc oxide nanoparticles can play a dual role here. They can prevent the premature leakage of drugs under physiological conditions. Moreover, Zn2+ produced after the decomposition of nanoparticles can act as a therapeutic agent, overcoming the tumor resistance to 5-FU and regulating a series of physiological reactions to inhibit tumor growth. It is worth noting that the porous ZIF-90 is an emerging drug carrier with a relatively high drug loading rate of 39% in this study. Synergistic 5-FU and ZnO nanoparticles have achieved tumor inhibition and have shown high therapeutic biosafety. Thus, the FZZ core-shell nanoparticles are a potential pH-controlled drug release system that can be applied to tumor treatment.
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Affiliation(s)
- Xiao Xiao
- State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China. and University of Science and Technology of China, Hefei, 230026, P. R. China
| | - Shuang Liang
- State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China. and University of Science and Technology of China, Hefei, 230026, P. R. China
| | - Yajie Zhao
- State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China. and University of Science and Technology of China, Hefei, 230026, P. R. China
| | - Dayu Huang
- State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.
| | - Bengang Xing
- Division of Chemistry and Biological Chemistry, School of Physical & Mathematical Sciences, Nanyang Technological University, Singapore 637371
| | - Ziyong Cheng
- State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China. and University of Science and Technology of China, Hefei, 230026, P. R. China
| | - Jun Lin
- State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China. and University of Science and Technology of China, Hefei, 230026, P. R. China
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20
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El-Zeiny HM, Abukhadra MR, Sayed OM, Osman AH, Ahmed SA. Insight into novel β-cyclodextrin-grafted-poly (N-vinylcaprolactam) nanogel structures as advanced carriers for 5-fluorouracil: Equilibrium behavior and pharmacokinetic modeling. Colloids Surf A Physicochem Eng Asp 2020. [DOI: 10.1016/j.colsurfa.2019.124197] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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21
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Abazari R, Ataei F, Morsali A, Slawin AMZ, L Carpenter-Warren C. A Luminescent Amine-Functionalized Metal-Organic Framework Conjugated with Folic Acid as a Targeted Biocompatible pH-Responsive Nanocarrier for Apoptosis Induction in Breast Cancer Cells. ACS APPLIED MATERIALS & INTERFACES 2019; 11:45442-45454. [PMID: 31718155 DOI: 10.1021/acsami.9b16473] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Folic acid amine-functionalized metal-organic framework (FOLA@NH2-Eu:TMU-62) with luminescent properties loaded with 5-fluorouracil (5-Fu), as an anticancer medication, was used to construct a new cancer targeted drug delivery system in the present study. The 5-Fu release from this targeted carrier along with MTT assay and trypan blue dye exclusion test results also exhibited pH-controlled characteristics of the given carrier in acidic environments, which is very suitable for targeting solid tumors. Then, the inhibitory action of 5-Fu-loaded FOLA@NH2-Eu:TMU-62 for Michigan Cancer Foundation-7 (MCF7) cell migration was explored according to scratch wound healing assays. Based on the results, the FOLA@NH2-Eu:TMU-62 carrier was not toxic for MCF-10A normal cells, but it was significantly toxic for MCF-7 breast cancer ones, revealing that the FOLA@NH2-Eu:TMU-62 carrier could be utilized in accurate cancer treatments through apoptotic pathways with higher reactive oxygen species compared with 5-Fu alone. This cancer-targeted design of FOLA@NH2-Eu:TMU-62 could thus pave the way for synergistic effects of targeting as well as organized release capabilities.
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Affiliation(s)
| | | | | | - Alexandra M Z Slawin
- School of Chemistry , University of St Andrews , St Andrews , Fife, KY16 9ST , U.K
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22
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Abukhadra MR, Refay NM, El-Sherbeeny AM, Mostafa AM, Elmeligy MA. Facile synthesis of bentonite/biopolymer composites as low-cost carriers for 5-fluorouracil drug; equilibrium studies and pharmacokinetic behavior. Int J Biol Macromol 2019; 141:721-731. [DOI: 10.1016/j.ijbiomac.2019.09.057] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 09/04/2019] [Accepted: 09/07/2019] [Indexed: 02/01/2023]
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23
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Taleblou N, Sirousazar M, Hassan ZM, Khaligh SG. Capecitabine-loaded anti-cancer nanocomposite hydrogel drug delivery systems: in vitro and in vivo efficacy against the 4T1 murine breast cancer cells. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2019; 31:72-92. [PMID: 31566505 DOI: 10.1080/09205063.2019.1675225] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
In this work, nanocomposite hydrogel drug delivery systems based on polyvinyl alcohol and montmorillonite loaded with the capecitabine, as an anti-cancer drug, were developed for oral administration. The gel fraction and swelling ability of the prepared nanocomposite hydrogels were experimentally measured. In vitro release kinetics of capecitabine in nanocomposite hydrogel drug delivery systems were studied. In vitro flow cytometry assay was utilized to exhibit the anti-cancer activity of the prepared nanocomposite hydrogel drug delivery systems against 4T1 cancer cell line. The anti-tumor efficacy of the nanocomposite hydrogel drug delivery systems was also studied in vivo on animal models. The results showed that the amount of montmorillonite incorporated into the nanocomposite hydrogel drug delivery systems could be recognized as a key parameter to adjust the values of the gel fraction, swelling and capecitabine release rate in a manner which by increasing the montmorillonite content, the gel fraction is increased while the swelling and drug release rate are decreased. The flow cytometry results demonstrated the better anti-cancer activity of the capecitabine-loaded nanocomposite hydrogel drug delivery systems as compared with the pure capecitabine. The in vivo assays indicated that the administration of nanocomposite hydrogel drug delivery systems had a significant effect on the reduction of the tumor growth in animal models as compared with pure capecitabine administration. In general, the prepared nanocomposite hydrogel drug delivery systems exhibited a suitable efficacy against 4T1 cancer cell line both in vitro and in vivo and they could be considered as promising candidates for controlled release of anti-cancer drugs in chemotherapy with enhanced therapeutic effects.
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Affiliation(s)
- Nastaran Taleblou
- Faculty of Chemical Engineering, Urmia University of Technology, Urmia, Iran
| | - Mohammad Sirousazar
- Faculty of Chemical Engineering, Urmia University of Technology, Urmia, Iran
| | - Zuhair Muhammad Hassan
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Sahar Ghaffari Khaligh
- Department of Pathology, Faculty of Veterinary Medicine, Semnan University, Semnan, Iran
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24
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Maney V, Singh M. The Synergism of Platinum-Gold Bimetallic Nanoconjugates Enhances 5-Fluorouracil Delivery In Vitro. Pharmaceutics 2019; 11:pharmaceutics11090439. [PMID: 31480562 PMCID: PMC6781313 DOI: 10.3390/pharmaceutics11090439] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Revised: 07/29/2019] [Accepted: 08/01/2019] [Indexed: 02/07/2023] Open
Abstract
Nanoparticle application has significantly impacted the field of medicine. The need to develop novel drugs with higher therapeutic potential has stimulated the development of innovative delivery strategies to mitigate the potent side effects associated with known chemotherapeutic drugs. This paper describes the synthesis of platinum-gold bimetallic nanoparticles (PtAuBNps), their functionalisation with chitosan, and entrapment of the anticancer drug 5-fluorouracil (5-FU). All PtAuBNps and their drug nanocomposites were physico-chemically characterised, displaying desirable properties with regards to shape, size (<120 nm) and colloidal stability. 5-FU binding and loading capacities in PtAuBNps were found to be 90.17% and 22.56%, respectively. In vitro cytotoxicity profiles determined using the MTT and SRB assays reflected up to 65% cell death in the MCF-7, HepG2 and Caco-2 cell lines. These nanocomposites exhibited excellent physiochemical attributes, high specificity towards cancer cells, with a pH-sensitive drug release in a simulated acidic tumour microenvironment through zero-order release kinetics. In addition, they possessed the potential to traverse the mucosal lining facilitating oral drug administration. Overall, 5-FU encapsulation improved the bioavailability of the drug in cancer cells, with the promise of enhancing its therapeutic effect, biocompatibility and safety. These positive results highlight PtAuBNps as promising in vitro delivery systems and merits future in vivo research.
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Affiliation(s)
- Vareessh Maney
- Nano-Gene and Drug Delivery Group, Discipline of Biochemistry, University of KwaZulu-Natal, Private Bag X54001, Durban, South Africa
| | - Moganavelli Singh
- Nano-Gene and Drug Delivery Group, Discipline of Biochemistry, University of KwaZulu-Natal, Private Bag X54001, Durban, South Africa.
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25
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Zhu LF, Zheng Y, Fan J, Yao Y, Ahmad Z, Chang MW. A novel core-shell nanofiber drug delivery system intended for the synergistic treatment of melanoma. Eur J Pharm Sci 2019; 137:105002. [DOI: 10.1016/j.ejps.2019.105002] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 07/09/2019] [Accepted: 07/10/2019] [Indexed: 12/31/2022]
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26
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Kevadiya BD, Chen L, Zhang L, Thomas MB, Davé RN. Fenofibrate Nanocrystal Composite Microparticles for Intestine-Specific Oral Drug Delivery System. Pharmaceuticals (Basel) 2019; 12:E109. [PMID: 31315263 PMCID: PMC6789785 DOI: 10.3390/ph12030109] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2019] [Revised: 07/09/2019] [Accepted: 07/10/2019] [Indexed: 11/16/2022] Open
Abstract
Hydrophobic drug nanocrystals (NCs) manufactured by particle engineering have been extensively investigated for enhanced oral bioavailability and therapeutic effectiveness. However, there are significant drawbacks, including fast dissolution of the nanocrystals in the gastric environment, leading to physicochemical instability. To solves this issue, we developed an innovative technique that involves the encapsulation of nanocrystals in composite spherical microparticles (NCSMs). Fenofibrate (FNB) NCs (FNB-NCs) manufactured by a wet stirred media milling (WSMM) technique and an ionotropic crosslinking method were used for FNB-NC encapsulation within gastroresistant NCSMs. Various solid-state methods were used for characterizing NCSMs. The pH-sensitive NCSMs showed a site-specific release pattern at alkaline pH and nearly 0% release at low pH (gastric environment). This phenomenon was confirmed by a real-time in situ UV-imaging system known as the surface dissolution imager (SDI), which was used to monitor drug release events by measuring the color intensity and concentration gradient formation. All these results proved that our NCSM approach is an innovative idea in oral drug delivery systems, as it resolves significant challenges in the intestine-specific release of hydrophobic drugs while avoiding fast dissolution or burst release.
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Affiliation(s)
- Bhavesh D Kevadiya
- New Jersey Center for Engineered Particulates, New Jersey Institute of Technology, Warren Street, Newark, NJ 07102, USA.
| | - Liang Chen
- New Jersey Center for Engineered Particulates, New Jersey Institute of Technology, Warren Street, Newark, NJ 07102, USA
| | - Lu Zhang
- New Jersey Center for Engineered Particulates, New Jersey Institute of Technology, Warren Street, Newark, NJ 07102, USA
| | - Midhun B Thomas
- Pandorum Technologies Pvt Ltd, Bangalore Bioinnovation Centre, Helix Biotech Park, Electronic City Phase 1, Bangalore, Karnataka 560100, India
| | - Rajesh N Davé
- New Jersey Center for Engineered Particulates, New Jersey Institute of Technology, Warren Street, Newark, NJ 07102, USA.
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Rutakhli A, Sabahi H, Riazi GH. Nanocomposite of montmorillonite/nettle extract: A potential ingredient for functional foods development. J Funct Foods 2019. [DOI: 10.1016/j.jff.2019.04.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
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28
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Šuleková M, Váhovská L, Hudák A, Žid L, Zeleňák V. A Study of 5-Fluorouracil Desorption from Mesoporous Silica by RP-UHPLC. Molecules 2019; 24:E1317. [PMID: 30987237 PMCID: PMC6479690 DOI: 10.3390/molecules24071317] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Revised: 04/01/2019] [Accepted: 04/01/2019] [Indexed: 02/04/2023] Open
Abstract
In cancer treatment, the safe delivery of the drug to the target tissue is an important task. 5-fluorouracil (5-FU), the well-known anticancer drug, was encapsulated into the pores of unmodified mesoporous silica SBA-15, as well as silica modified with 3-aminopropyl and cyclohexyl groups. The drug release studies were performed in two different media, in a simulated gastric fluid (pH = 2) and in a simulated body fluid (pH = 7) by RP-UHPLC. The simple and rapid RP-UHPLC method for quantitative determination of 5-fluorouracil released from unmodified and modified mesoporous silica SBA-15 was established on ODS Hypersil C18 column (150 × 4.6 mm, 5 µm) eluted with mobile phase consisted of methanol: phosphate buffer in volume ratio of 3:97 (v/v). Separation was achieved by isocratic elution. The flow rate was kept at 1 mL/min, the injection volume was set at 20 µL and the column oven temperature was maintained at 25 °C. The effluent was monitored at 268 nm. This paper provides information about the quantitative determination of the released 5-FU from silica. It was found out that larger amount of the drug was released in neutral pH in comparison with the acidic medium. In addition, surface functionalisation of silica SBA-15 influences the release properties of the drug.
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Affiliation(s)
- Monika Šuleková
- Department of Chemistry, Biochemistry and Biophysics, Institute of Pharmaceutical Chemistry, The University of Veterinary Medicine and Pharmacy in Košice, 041 81 Košice, Slovakia.
| | - Lucia Váhovská
- Department of Chemistry, Biochemistry and Biophysics, Institute of Biochemistry, The University of Veterinary Medicine and Pharmacy in Košice, 041 81 Košice, Slovakia.
| | - Alexander Hudák
- Department of Chemistry, Biochemistry and Biophysics, Institute of Pharmaceutical Chemistry, The University of Veterinary Medicine and Pharmacy in Košice, 041 81 Košice, Slovakia.
| | - Lukáš Žid
- Department of Inorganic Chemistry, Faculty of Sciences, P. J. Šafárik University, Moyzesova 11, SK-041 54 Košice, Slovakia.
| | - Vladimír Zeleňák
- Department of Inorganic Chemistry, Faculty of Sciences, P. J. Šafárik University, Moyzesova 11, SK-041 54 Košice, Slovakia.
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29
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Research on 5-fluorouracil as a drug carrier materials with its in vitro release properties on organic modified magadiite. Eur J Pharm Sci 2019; 130:44-53. [PMID: 30660800 DOI: 10.1016/j.ejps.2019.01.017] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Revised: 12/03/2018] [Accepted: 01/15/2019] [Indexed: 11/24/2022]
Abstract
The magadiite (MAG) was modified by cetyltrimethyl ammonium-Bromide (CTAB) and then further modified by Chitosan (CS) which is called organic modified-magadiite as magadiite-cetyltrimethyl ammonium bromide (MAG-CTAB) and magadiite-cetyltrimethyl ammonium bromide-Chitosan (MAG-CTAB-CS), respectively, in this research study. The MAG, MAG-CTAB, and MAG-CTAB-CS were used as 5-Fluorouracil (5-FU) drug carrier materials; the drug carrier's materials were marked as magadiite-5-Fluorouracil (MAG/5-FU), magadiite-cetyltrimethyl ammonium bromide-5-Fluorouracil (MAG-CTAB/5-FU), and magadiite-cetyltrimethyl ammonium bromide-Chitosan (MAG-CTAB-CS/5-FU). X-ray diffraction(XRD, Flourier transform infrared spectrometry (FTIR) and scanning electron microscopy (SEM) results were shown that 5-Fluorouracil was combined with carrier materials through physical apparent adsorption, ion exchange, chemical bond, hydrogen bond, and electrostatic interaction. The drug carriers in vitro release behavior in simulated gastric fluids (SGF，pH = 1.35) and intestinal fluids (SIF，pH = 7.40) were investigated. The drug loading capacity and accumulated release ration were as follows the order: MAG-CTAB-CS/5-FU > MAG-CTAB/5-FU > MAG/5-FU. The drug loading capacity of MAG-CTAB-CS/5-FU was 162.29 mg/g, 48 h later the drug accumulated release ratio was 61.24%, and the release amount was 97.52 mg/g for 24 h. Korsmeyer-Peppas model and First order model were found to be suitable to describe the vitro release behavior of 5-Fluorouracil. This would be an economically viable and efficient method for the preparation of advanced drug delivery system.
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30
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Li L, Zhang R, Gu W, Xu ZP. Mannose-conjugated layered double hydroxide nanocomposite for targeted siRNA delivery to enhance cancer therapy. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2018. [DOI: 10.1016/j.nano.2017.06.006] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
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31
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Dening TJ, Thomas N, Rao S, van Looveren C, Cuyckens F, Holm R, Prestidge CA. Montmorillonite and Laponite Clay Materials for the Solidification of Lipid-Based Formulations for the Basic Drug Blonanserin: In Vitro and in Vivo Investigations. Mol Pharm 2018; 15:4148-4160. [PMID: 30067372 DOI: 10.1021/acs.molpharmaceut.8b00555] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Solid-state lipid-based formulations offer great potential for the improved oral delivery of poorly water-soluble drugs. This study investigates the use of the high-surface-area clay materials, montmorillonite and laponite, as solid carriers for lipid-based formulations. The unique cation-exchange properties of clay platelets were exploited to preload the ionizable hydrophobic compound, blonanserin, prior to encapsulating a drug-loaded lipid solution. Thus, solid-state lipid-based formulations with dual-loading capabilities were developed and studied. These formulations were compared with simple clay-based lipid formulations, where blonanserin was loaded in the lipid phase only. The drug release behavior of all clay-based formulations was assessed during in vitro dissolution studies under simulated gastric conditions and in vitro fasting intestinal lipolysis studies. Montmorillonite- and laponite-based lipid formulations significantly reduced blonanserin solubilization relative to a control lipid solution and silica-lipid hybrid particles, owing to incomplete drug release from the clay cation-exchange sites. This phenomenon was replicated during in vivo pharmacokinetic studies, whereby the bioavailability of simple clay-based lipid formulations was decreased relative to controls. Importantly, the solid-state dual-loaded montmorillonite-based lipid formulation provided an optimal pharmacokinetic performance, achieving the same degree of bioavailability enhancement as the control lipid solution. These findings indicate the potential of solid-state dual-loaded clay-based lipid formulations for increasing drug loading levels and enhancing the oral absorption of poorly soluble weak base compounds.
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Affiliation(s)
| | | | | | | | | | - René Holm
- Department of Science and Environment , Roskilde University , 4000 Roskilde , Denmark
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Inexpensive Apparatus for Fabricating Microspheres for 5-Fluorouracil Controlled Release Systems. INTERNATIONAL JOURNAL OF CHEMICAL ENGINEERING 2018. [DOI: 10.1155/2018/2340249] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
The aim of this study was to develop an inexpensive apparatus for fabricating microspheres, based on chitosan, for 5-fluorouracil (5-FU) controlled release. Chitosan microspheres were prepared by precipitation method and the effects of manufacturing parameters (injection and airflow rates) on size distribution microspheres were analyzed by optical and scanning electron microscopy. The results show that the manufacturing parameters, injection and airflow rates, determine the microsphere size distribution. By modulating these parameters, it was possible to produce chitosan microspheres as small as 437 ± 44 μm and as large as 993 ± 18 μm. Chitosan microspheres loaded with 5-FU were also produced using the experimental equipment. The obtained microspheres presented 5-FU controlled release, indicating that the microspheres can be used orally, since they are capable of crossing the stomach barrier and of continuing with the process of 5-FU release.
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Ashour AE, Badran MM, Kumar A, Rishi AK, Yassin AE. Di-Block PLCL and Tri-Block PLCLG Matrix Polymeric Nanoparticles Enhanced the Anticancer Activity of Loaded 5-Fluorouracil. IEEE Trans Nanobioscience 2017; 15:739-747. [PMID: 28029617 DOI: 10.1109/tnb.2016.2612340] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
In the current study, 5-FU-loaded nanoparticles (NPs) were prepared using polylactic-co-glycolic acid (PLGA), polycaprolactone (PCL), di-block poly lactide-co-caprolactone (PLCL) and tri-block poly L-lactide-co-caprolactone-co-glycolide (PLCLG). The influence of these polymers on the particle sizes, morphology, drug loading, and in vitro drug release was investigated. The anticancer activity was assessed utilizing MTT assay in three human cancer cell lines of different tissue origin; brain (Daoy), liver (HepG2), and colorectal (HT29) using suitable negative and positive controls. The prepared NPs showed a uniform spherical shape with an average size range of 193.5± 6.3 to 303.5± 3.3 nm with negative zeta potential. The entrapment efficiency achieved with F4-F6 (block copolymer NPs) was 78-79% and significantly higher compared with F1 PLGA (31%) and F2; PCL (37%). An initial rapid 5-FU release followed by a slow release ranging from 35% to 81% after 72 h was observed. All the prepared NPs formulations showed enhancement in the cytotoxicity of 5-FU towards all the three cancer cell lines. Generally, block copolymer NPs (F4-F6) showed higher % cell death over PLGA (F1) and PCL (F2) NPs after 48 and 72 h incubation in the case of HepG2 and HT-29. The incorporation of PEG with the tri-block (F6) caused a significant increase in the cytotoxicity of NPs in all of the three cancer cell lines. Block copolymer-based NPs can be considered as promising carriers for enhancing the efficacy of 5-FU in cancer therapy.
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35
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Huang Y, Tao Q, Hou D, Hu S, Tian S, Chen Y, Gui R, Yang L, Wang Y. A novel ion-exchange carrier based upon liposome-encapsulated montmorillonite for ophthalmic delivery of betaxolol hydrochloride. Int J Nanomedicine 2017; 12:1731-1745. [PMID: 28280338 PMCID: PMC5340245 DOI: 10.2147/ijn.s122747] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
As a novel ion-exchange carrier with high surface area and excellent exchangeability, montmorillonite (Mt) was intercalated with betaxolol hydrochloride (BH) to form a nanocomposite and then encapsulated by liposomes (Mt-BH-LPs) for an ophthalmic drug-delivery system. The Mt-BH and Mt-BH-LPs were prepared by an acidification process and ethanol injection combined with ammonium sulfate gradient methods. The successful formation of Mt-BH and Mt-BH-LPs was verified by thermogravimetric analysis, X-ray diffraction, Fourier-transform infrared spectra, and transmission electron microscopy. Mt-BH-LPs possessed the favorable physical characteristics of encapsulation efficiency, drug loading, mean particle size, and ζ-potential. In vitro release studies indicated Mt-BH-LPs effectively maintained a relatively sustained slow release. Immortalized human corneal epithelial cell cytotoxicity, in vivo rabbit eye-irritation tests, and chorioallantoic membrane–trypan blue staining all revealed that Mt-BH-LPs had no obvious irritation on ocular tissues. A new in vitro tear-turnover model, including inserts containing human corneal epithelial cells, was designed to evaluate the precorneal retention time of Mt-BH-LPs. The results showed that Mt-BH-LPs maintained a certain BH concentration in tear fluid for a longer period than the BH solution. In vivo precorneal retention studies also indicated Mt-BH-LPs prolonged drug retention on the ocular surface more than the BH solution. Furthermore, pharmacodynamic studies showed that Mt-BH-LPs had a prolonged effect on decreasing intraocular optical pressure in rabbits. Our results demonstrated that Mt-BH-LPs have potential as an ophthalmic delivery system.
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Affiliation(s)
- Yi Huang
- College of Pharmacy, Guangdong Pharmaceutical University
| | - Qi Tao
- Key Laboratory of Mineralogy and Metallogeny, Chinese Academy of Sciences, Guangdong Provincial Key Laboratory of Mineral Physics and Materials
| | - Dongzhi Hou
- College of Pharmacy, Guangdong Pharmaceutical University
| | - Sheng Hu
- College of Pharmacy, Guangdong Pharmaceutical University
| | - Shuangyan Tian
- College of Pharmacy, Guangdong Pharmaceutical University
| | - Yanzhong Chen
- Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou
| | - Ruyi Gui
- College of Pharmacy, Guangdong Pharmaceutical University
| | - Lingling Yang
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences
| | - Yao Wang
- Qingdao Eye Hospital, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China
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36
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Karataş D, Tekin A, Bahadori F, Çelik MS. Interaction of curcumin in a drug delivery system including a composite with poly(lactic-co-glycolic acid) and montmorillonite: a density functional theory and molecular dynamics study. J Mater Chem B 2017; 5:8070-8082. [DOI: 10.1039/c7tb01964e] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Curcumin as an anticancer agent can be delivered with a composite including poly(lactic-co-glycolic acid) and montmorillonite.
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Affiliation(s)
- D. Karataş
- Istanbul Technical University
- Mineral Processing Engineering Department
- 34469 Maslak
- Turkey
| | - A. Tekin
- Informatics Institute
- Istanbul Technical University
- 34469 Maslak
- Turkey
| | - F. Bahadori
- Department of Pharmaceutical Biotechnology
- Faculty of Pharmacy
- Bezmialem Vakif University
- Fatih
- Turkey
| | - M. S. Çelik
- Istanbul Technical University
- Mineral Processing Engineering Department
- 34469 Maslak
- Turkey
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37
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Hellrup J, Holmboe M, Nartowski KP, Khimyak YZ, Mahlin D. Structure and Mobility of Lactose in Lactose/Sodium Montmorillonite Nanocomposites. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2016; 32:13214-13225. [PMID: 27951698 DOI: 10.1021/acs.langmuir.6b01967] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
This study aims at investigating the molecular level organization and molecular mobility in montmorillonite nanocomposites with the uncharged organic low-molecular-weight compound lactose commonly used in pharmaceutical drug delivery, food technology, and flavoring. Nanocomposites were prepared under slow and fast drying conditions, attained by drying at ambient conditions and by spray-drying, respectively. A detailed structural investigation was performed with modulated differential scanning calorimetry, powder X-ray diffraction, solid-state nuclear magnetic resonance spectroscopy, scanning electron microscopy, microcalorimetry, and molecular dynamics simulations. The lactose was intercalated in the sodium montmorillonite interlayer space regardless of the clay content, drying rate, or humidity exposure. Although, the spray-drying resulted in higher proportion of intercalated lactose compared with the drying under ambient conditions, nonintercalated lactose was present at 20 wt % lactose content and above. This indicates limitations in maximum loading capacity of nonionic organic substances into the montmorillonite interlayer space. Furthermore, a fraction of the intercalated lactose in the co-spray-dried nanocomposites diffused out from the clay interlayer space upon humidity exposure. Also, the lactose in the nanocomposites demonstrated higher molecular mobility than that of neat amorphous lactose. This study provides a foundation for understanding functional properties of lactose/Na-MMT nanocomposites, such as loading capacity and physical stability.
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Affiliation(s)
- Joel Hellrup
- Department of Pharmacy, Uppsala University , 751 23 Uppsala, Sweden
| | - Michael Holmboe
- Department of Chemistry, Umeå University , 907 36 Umeå, Sweden
| | - Karol P Nartowski
- School of Pharmacy, University of East Anglia , Norwich Research Park, Norwich NR4 7TJ, United Kingdom
| | - Yaroslav Z Khimyak
- School of Pharmacy, University of East Anglia , Norwich Research Park, Norwich NR4 7TJ, United Kingdom
| | - Denny Mahlin
- Department of Pharmacy, Uppsala University , 751 23 Uppsala, Sweden
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38
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Gajski G, Gerić M, Domijan AM, Garaj-Vrhovac V. Combined cyto/genotoxic activity of a selected antineoplastic drug mixture in human circulating blood cells. CHEMOSPHERE 2016; 165:529-538. [PMID: 27681109 DOI: 10.1016/j.chemosphere.2016.09.058] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Revised: 09/06/2016] [Accepted: 09/14/2016] [Indexed: 06/06/2023]
Abstract
Antineoplastic drugs are highly cytotoxic chemotherapeutic agents that can often interfere directly or indirectly with the cell's genome. In an environmental or medical setting simultaneous exposure may occur. Such multiple exposures may pose a higher risk than it could be assumed from the studies evaluating the effect of a single substance. Therefore, in the present study we tested the combined cyto/genotoxicity of a mixture of selected antineoplastic drugs with different mechanisms of action (5-fluorouracil, etoposide, and imatinib mesylate) towards human lymphocytes in vitro. The results suggest that the selected antineoplastic drug mixture is potentially cyto/genotoxic and that it can induce cell and genome damage even at low concentrations. Moreover, the changes in the measured oxidative stress parameters suggest the participation of reactive oxygen species in the cyto/genotoxicity of the selected mixture. The obtained results indicate not only that such mixtures may pose a risk to cell and genome integrity, but also that single compound toxicity data are not sufficient for the predicting toxicity in a complex environment. Altogether, the results emphasise the need for further toxicological screening of antineoplastic drug mixtures, especially at low environmentally relevant concentrations, as to avoid any possible adverse effects on the environment and human health.
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Affiliation(s)
- Goran Gajski
- Institute for Medical Research and Occupational Health, Mutagenesis Unit, Ksaverska cesta 2, 10000 Zagreb, Croatia.
| | - Marko Gerić
- Institute for Medical Research and Occupational Health, Mutagenesis Unit, Ksaverska cesta 2, 10000 Zagreb, Croatia.
| | - Ana-Marija Domijan
- University of Zagreb, Faculty of Pharmacy and Biochemistry, A. Kovačića 1, 10000 Zagreb, Croatia.
| | - Vera Garaj-Vrhovac
- Institute for Medical Research and Occupational Health, Mutagenesis Unit, Ksaverska cesta 2, 10000 Zagreb, Croatia.
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Layered nanohydroxyapatite as a novel nanocarrier for controlled delivery of 5-fluorouracil. Int J Pharm 2016; 513:17-25. [DOI: 10.1016/j.ijpharm.2016.09.004] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Revised: 06/24/2016] [Accepted: 09/02/2016] [Indexed: 01/01/2023]
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40
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Reddy AB, Manjula B, Jayaramudu T, Sadiku ER, Anand Babu P, Periyar Selvam S. 5-Fluorouracil Loaded Chitosan-PVA/Na +MMT Nanocomposite Films for Drug Release and Antimicrobial Activity. NANO-MICRO LETTERS 2016; 8:260-269. [PMID: 30460286 PMCID: PMC6223683 DOI: 10.1007/s40820-016-0086-4] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/26/2015] [Accepted: 02/05/2016] [Indexed: 05/30/2023]
Abstract
In the present study, chitosan and polyvinyl alcohol (PVA) were blended with different concentrations of sodium montmorillonite (Na+MMT) clay solution by a solvent casting method. X-ray diffraction and transition electron microscope results show that the film properties are related to the co-existence of Na+MMT intercalation/exfoliation in the blend and the interaction between chitosan-PVA and Na+MMT. 5-Fluorouracil (5-FU) was loaded with chitosan-PVA/Na+MMT nanocomposite films for in vitro drug delivery study. The antimicrobial activity of the chitosan-PVA/Na+MMT films showed significant effect against Salmonella (Gram-negative) and Staphylococcus aureus (Gram-positive), whereas 5-FU encapsulated chitosan-PVA/Na+MMT bio-nanocomposite films did not show any inhibition against bacteria. Our results indicate that combination of a flexible and soft polymeric material with high drug loading ability of a hard inorganic porous material can produce improved control over degradation and drug release. It will be an economically viable method for preparation of advanced drug delivery vehicles and biodegradable implants or scaffolds.
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Affiliation(s)
- A. Babul Reddy
- Department of Chemical, Metallurgical and Materials Engineering, Tshwane University of Technology, CSIR Campus, Building 14D, Lynwood Ridge, Private Bag X025, Pretoria, 0040 South Africa
| | - B. Manjula
- Department of Chemical, Metallurgical and Materials Engineering, Tshwane University of Technology, CSIR Campus, Building 14D, Lynwood Ridge, Private Bag X025, Pretoria, 0040 South Africa
| | - T. Jayaramudu
- Department of Chemical, Metallurgical and Materials Engineering, Tshwane University of Technology, CSIR Campus, Building 14D, Lynwood Ridge, Private Bag X025, Pretoria, 0040 South Africa
| | - E. R. Sadiku
- Department of Chemical, Metallurgical and Materials Engineering, Tshwane University of Technology, CSIR Campus, Building 14D, Lynwood Ridge, Private Bag X025, Pretoria, 0040 South Africa
| | - P. Anand Babu
- Department of Food Process Engineering, School of Bioengineering, SRM University, Kattankulathur, Tamil Nadu 603203 India
| | - S. Periyar Selvam
- Department of Food Process Engineering, School of Bioengineering, SRM University, Kattankulathur, Tamil Nadu 603203 India
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41
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Kumar GP, Sanganal JS, Phani A, Manohara C, Tripathi SM, Raghavendra H, Janardhana P, Amaresha S, Swamy K, Prasad R. Anti-cancerous efficacy and pharmacokinetics of 6-mercaptopurine loaded chitosan nanoparticles. Pharmacol Res 2015; 100:47-57. [DOI: 10.1016/j.phrs.2015.07.025] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Revised: 07/26/2015] [Accepted: 07/26/2015] [Indexed: 11/29/2022]
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Tseng CL, Chen JC, Wu YC, Fang HW, Lin FH, Tang TP. Development of lattice-inserted 5-Fluorouracil-hydroxyapatite nanoparticles as a chemotherapeutic delivery system. J Biomater Appl 2015; 30:388-97. [DOI: 10.1177/0885328215588307] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Developing an effective vehicle for cancer treatment, hydroxyapatite nanoparticles were fabricated for drug delivery. When 5-Fluorouracil, a major chemoagent, is combined with hydroxyapatite nanocarriers by interclay insertion, the modified hydroxyapatite nanoparticles have superior lysosomal degradation profiles, which could be leveraged as controlled drug release. The decomposition of the hydroxyapatite nanocarriers facilitates the release of 5-Fluorouracil into the cytoplasm causing cell death. Hydroxyapatite nanoparticles with/without 5-Fluorouracil were synthesized and analyzed in this study. Their crystallization properties and chemical composition were examined by X-ray diffraction and Fourier transforms infrared spectroscopy. The 5-Fluorouracil release rate was determined by UV spectroscopy. The biocompatibility of hydroxyapatite-5-Fluorouracil extraction solution was assessed using 3T3 cells via a WST-8 assay. The effect of hydroxyapatite-5-Fluorouracil particles which directly work on the human lung adenocarcinoma (A549) cells was evaluated by a lactate dehydrogenase assay via contact cultivation. A 5-Fluorouracil-absorbed hydroxyapatite particles were also tested. Overall, hydroxyapatite-5-Fluorouracils were prepared using a co-precipitation method wherein 5-Fluorouracil was intercalated in the hydroxyapatite lattice as determined by X-ray diffraction. Energy dispersive scanning examination showed the 5-Fluorouracil content was higher in hydroxyapatite-5-Fluorouracil than in a prepared absorption formulation. With 5-Fluorouracil insertion in the lattice, the widths of the a and c axial constants of the hydroxyapatite crystal increased. The extraction solution of hydroxyapatite-5-Fluorouracil was nontoxic to 3T3 cells, in which 5-Fluorouracil was not released in a neutral phosphate buffer solution. In contrast, at a lower pH value (2.5), 5-Fluorouracil was released by the acidic decomposition of hydroxyapatite. Finally, the results of the lactate dehydrogenase assay revealed that 5-Fluorouracil-hydroxyapatite was highly toxic to A549 cells through direct culture, this phenomenon may result from lysosomal decomposition of particles causing 5-Fluorouracil releasing. The pH-responsive hydroxyapatite-5-Fluorouracil nanoparticles have the potential to be part of a selective drug-delivery system in chemotherapy for cancer treatment.
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Affiliation(s)
- Ching-Li Tseng
- Graduate Institute of Biomedical Materials and Tissue Engineering, College of Oral Medicine, Taipei Medical University, Taipei City, Taiwan
| | - Jung-Chih Chen
- Institute of Biomedical Engineering, National Chiao Tung University, Hsinchu City, Taiwan
| | - Yu-Chun Wu
- Institute of Materials Science and Engineering, National Taipei University of Technology, Taipei City, Taiwan
| | - Hsu-Wei Fang
- Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei City, Taiwan
- Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli County, Taiwan
| | - Feng-Huei Lin
- Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli County, Taiwan
- Institute of Biomedical Engineering, National Taiwan University, Taipei City, Taiwan
| | - Tzu-Piao Tang
- Institute of Materials Science and Engineering, National Taipei University of Technology, Taipei City, Taiwan
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43
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Bello ML, Junior AM, Vieira BA, Dias LRS, de Sousa VP, Castro HC, Rodrigues CR, Cabral LM. Sodium montmorillonite/amine-containing drugs complexes: new insights on intercalated drugs arrangement into layered carrier material. PLoS One 2015; 10:e0121110. [PMID: 25803292 PMCID: PMC4372448 DOI: 10.1371/journal.pone.0121110] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2014] [Accepted: 01/28/2015] [Indexed: 01/11/2023] Open
Abstract
Layered drug delivery carriers are current targets of nanotechnology studies since they are able to accommodate pharmacologically active substances and are effective at modulating drug release. Sodium montmorillonite (Na-MMT) is a clay that has suitable properties for developing new pharmaceutical materials due to its high degree of surface area and high capacity for cation exchange. Therefore Na-MMT is a versatile material for the preparation of new drug delivery systems, especially for slow release of protonable drugs. Herein, we describe the intercalation of several amine-containing drugs with Na-MMT so we can derive a better understanding of how these drugs molecules interact with and distribute throughout the Na-MMT interlayer space. Therefore, for this purpose nine sodium montmorillonite/amine-containing drugs complexes (Na-MMT/drug) were prepared and characterized. In addition, the physicochemical properties of the drugs molecules in combination with different experimental conditions were assessed to determine how these factors influenced experimental outcomes (e.g. increase of the interlayer spacing versus drugs arrangement and orientation). We also performed a molecular modeling study of these amine-containing drugs associated with different Na-MMT/drug complex models to analyze the orientation and arrangement of the drugs molecules in the complexes studied. Six amine-containing drugs (rivastigmine, doxazosin, 5-fluorouracil, chlorhexidine, dapsone, nystatin) were found to successfully intercalate Na-MMT. These findings provide important insights on the interlayer aspect of the molecular systems formed and may contribute to produce more efficient drug delivery nanosystems.
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Affiliation(s)
- Murilo L. Bello
- Laboratório de Modelagem Molecular e QSAR (ModMolQSAR), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Aridio M. Junior
- Laboratório de Tecnologia Farmacêutica Industrial (LabTIF), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Bárbara A. Vieira
- Laboratório de Modelagem Molecular e QSAR (ModMolQSAR), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Luiza R. S. Dias
- Laboratório de Química Medicinal (LQMed), Faculdade de Farmácia, Universidade Federal Fluminense, RJ, Brazil
| | - Valéria P. de Sousa
- Laboratório de Tecnologia Farmacêutica Industrial (LabTIF), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Helena C. Castro
- LABiEMol, Instituto de Biologia, Universidade Federal Fluminense, Niterói, RJ, Brazil
| | - Carlos R. Rodrigues
- Laboratório de Modelagem Molecular e QSAR (ModMolQSAR), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Lucio M. Cabral
- Laboratório de Tecnologia Farmacêutica Industrial (LabTIF), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
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Abstract
Samples of zeolite ZSM-5 have been synthesized in both the sodium form (ZSM-5) and the acid activated form (H-ZSM-5). In addition, each of these two forms was prepared in the two molar SiO2/Al2O3ratios of 169 and 15. All samples of these ZSM-5 derivatives were characterized by X-ray diffraction (XRD), nitrogen adsorption-desorption isotherms, thermal gravimetric analysis (TGA), X-ray fluorescence (XRF), and scanning electron microscopy (SEM). The samples were successfully loaded with the anticancer drug 5-fluorouracil (5-FU) with loading capacities varying from 22% (for the sodium form having the lower molar SiO2/Al2O3ratio of 15, ZSM-5-(15)) to 43% (for the corresponding acid form, H-ZSM-5-(15)). Percent release of the drug-loaded ZSM-5 samples into simulated body fluid (SBF) was measured at pH 7.4 and 37°C. The results showed a slight variation in the % release within the range 84–93%, while the first-order rate constant (k) varied from 2.2 h−1for ZSM-5-(15) to 3.9 h−1for H-ZSM-5-(15). It was interesting to note that at the higher molar SiO2/Al2O3ratios of 169, both the sodium form, ZSM-5-(169), and the acid form, H-ZSM-5-(169), exhibit an intermediate efficiency in either % loading (38%) or first-order kinetic release constant (k= 2.9 h−1).
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45
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Nasr M, Ghorab MK, Abdelazem A. In vitro and in vivo evaluation of cubosomes containing 5-fluorouracil for liver targeting. Acta Pharm Sin B 2015; 5:79-88. [PMID: 26579429 PMCID: PMC4629209 DOI: 10.1016/j.apsb.2014.12.001] [Citation(s) in RCA: 135] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2014] [Revised: 11/04/2014] [Accepted: 11/28/2014] [Indexed: 01/02/2023] Open
Abstract
The objective of this study was to prepare cubosomal nanoparticles containing a hydrophilic anticancer drug 5-fluorouracil (5-FU) for liver targeting. Cubosomal dispersions were prepared by disrupting a cubic gel phase of monoolein and water in the presence of Poloxamer 407 as a stabilizer. Cubosomes loaded with 5-FU were characterized in vitro and in vivo. In vitro, 5-FU-loaded cubosomes entrapped 31.21% drug and revealed nanometer-sized particles with a narrow particle size distribution. In vitro 5-FU release from cubosomes exhibited a phase of rapid release of about half of the entrapped drug during the first hour, followed by a relatively slower drug release as compared to 5-FU solution. In vivo biodistribution experiments indicated that the cubosomal formulation significantly (P<0.05) increased 5-FU liver concentration, a value approximately 5-fold greater than that observed with a 5-FU solution. However, serum serological results and histopathological findings revealed greater hepatocellular damage in rats treated with cubosomal formulation. These results demonstrate the successful development of cubosomal nanoparticles containing 5-FU for liver targeting. However, further studies are required to evaluate hepatotoxicity and in vivo antitumor activity of lower doses of 5-FU cubosomal formulation in treatment of liver cancer.
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Affiliation(s)
- Mohamed Nasr
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Cairo 11790, Egypt
- Corresponding author. Tel.: +20 2010 1668824.
| | - Mohamed K. Ghorab
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Cairo 11790, Egypt
| | - Ahmed Abdelazem
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo 11790, Egypt
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46
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Subramanian AP, Jaganathan SK, Supriyanto E. Overview on in vitro and in vivo investigations of nanocomposite based cancer diagnosis and therapeutics. RSC Adv 2015. [DOI: 10.1039/c5ra11912j] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
The nanodevices are synthesized using nanocomposites by the researchers around the globe. Most of their applications are related to in vivo visualization and therapy with anticancer drugs in the field of oncology.
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Affiliation(s)
- A. P. Subramanian
- IJN-UTM Cardiovascular Engineering Centre
- Faculty of Biosciences and Medical Engineering
- Universiti Teknologi Malaysia
- Johor Bahru 81310
- Malaysia
| | - S. K. Jaganathan
- IJN-UTM Cardiovascular Engineering Centre
- Faculty of Biosciences and Medical Engineering
- Universiti Teknologi Malaysia
- Johor Bahru 81310
- Malaysia
| | - Eko Supriyanto
- IJN-UTM Cardiovascular Engineering Centre
- Faculty of Biosciences and Medical Engineering
- Universiti Teknologi Malaysia
- Johor Bahru 81310
- Malaysia
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47
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Yu M, Pan L, Sun L, Li J, Shang J, Zhang S, Liu D, Li W. Supramolecular assemblies constructed from β-cyclodextrin-modified montmorillonite nanosheets as carriers for 5-fluorouracil. J Mater Chem B 2015; 3:9043-9052. [DOI: 10.1039/c5tb01513h] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
5-Fluorouracil-loaded supramolecular assemblies formed from self-assembling β-cyclodextrin modified montmorillonite nanosheets exhibit better antitumor activity and lower cytotoxicity in vitro.
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Affiliation(s)
- Mingan Yu
- Department of Medicinal Chemistry
- School of Pharmacy
- Chongqing Medical University
- Chongqing 400016
- P. R. China
| | - Lijun Pan
- Pharmaceutical Teaching Laboratory
- Chongqing Medical University
- Chongqing 400016
- P. R. China
| | - Lili Sun
- Department of Medicinal Chemistry
- School of Pharmacy
- Chongqing Medical University
- Chongqing 400016
- P. R. China
| | - Jing Li
- Department of Medicinal Chemistry
- School of Pharmacy
- Chongqing Medical University
- Chongqing 400016
- P. R. China
| | - Jingchuan Shang
- Department of Pharmaceutical Analysis
- School of Pharmacy
- Chongqing Medical University
- Chongqing 400016
- P. R. China
| | - Shurong Zhang
- Department of Medicinal Chemistry
- School of Pharmacy
- Chongqing Medical University
- Chongqing 400016
- P. R. China
| | - Duqiang Liu
- Department of Medicinal Chemistry
- School of Pharmacy
- Chongqing Medical University
- Chongqing 400016
- P. R. China
| | - Wei Li
- Department of Medicinal Chemistry
- School of Pharmacy
- Chongqing Medical University
- Chongqing 400016
- P. R. China
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Li W, Sun L, Pan L, Lan Z, Jiang T, Yang X, Luo J, Li R, Tan L, Zhang S, Yu M. Dendrimer-like assemblies based on organoclays as multi-host system for sustained drug delivery. Eur J Pharm Biopharm 2014; 88:706-17. [PMID: 25308929 DOI: 10.1016/j.ejpb.2014.09.014] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2014] [Revised: 09/22/2014] [Accepted: 09/25/2014] [Indexed: 12/20/2022]
Abstract
Chemical modification of nanoclay will ensure further progress on these materials. In this work, we show that montmorillonite (MTM) nanosheets can be modified with β-cyclodextrin (CD) via a nucleophilic substitution reaction between mono-6-(p-toluenesulfonyl)-6-deoxy-β-CD and an amino group of 3-aminopropyltriethoxysilane (APTES)-functionalized MTM. The resulting MTM-APTES-CD can be further self-assembled into dendrimer-like assemblies, exhibit a well-dispersed property even in Dulbecco's phosphate-buffered saline and do not aggregate for a period of at least 20days. The structure, morphology and assembly mechanism are systematically studied by (29)Si MAS NMR, FT-IR, (1)H NMR, SEM, FE-TEM, DLS and AFM, and the change in assemblies during the drug release is monitored using FE-TEM images. MTT assays indicate that the assemblies only have low cytotoxicity, while CLSM and TEM observations reveal that the assemblies can easily penetrate cultured human endothelial cells. When clopidogrel is used as a guest molecule, the assemblies show not only much higher loading capacities compared to MTM and other containing β-CD assemblies or nanoparticles, but also a sustained release of clopidogrel up to 30days. This is attributed to the fact that the guest molecule is both supramolecularly complexed within the dendritic scaffold and intercalated into CD and MTM hosts. Host-guest systems between assemblies and various guests hold promising applications in drug delivery system and in the biomedical fields.
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Affiliation(s)
- Wei Li
- Department of Medicinal Chemistry, School of Pharmacy, Chongqing Medical University, Chongqing, PR China; Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing, PR China
| | - Lili Sun
- Department of Medicinal Chemistry, School of Pharmacy, Chongqing Medical University, Chongqing, PR China
| | - Lijun Pan
- Pharmaceutical Teaching Laboratory, Chongqing Medical University, Chongqing, PR China
| | - Zuopin Lan
- Department of Medicinal Chemistry, School of Pharmacy, Chongqing Medical University, Chongqing, PR China
| | - Tao Jiang
- Department of Medicinal Chemistry, School of Pharmacy, Chongqing Medical University, Chongqing, PR China
| | - Xiaolan Yang
- College of Laboratory Medicine, Chongqing Medical University, Chongqing, PR China
| | - Jianchun Luo
- Department of Medicinal Chemistry, School of Pharmacy, Chongqing Medical University, Chongqing, PR China
| | - Ronghua Li
- Department of Medicinal Chemistry, School of Pharmacy, Chongqing Medical University, Chongqing, PR China
| | - Liqing Tan
- Department of Medicinal Chemistry, School of Pharmacy, Chongqing Medical University, Chongqing, PR China
| | - Shurong Zhang
- Department of Medicinal Chemistry, School of Pharmacy, Chongqing Medical University, Chongqing, PR China
| | - Mingan Yu
- Department of Medicinal Chemistry, School of Pharmacy, Chongqing Medical University, Chongqing, PR China.
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49
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Kevadiya BD, Rajkumar S, Bajaj HC, Chettiar SS, Gosai K, Brahmbhatt H, Bhatt AS, Barvaliya YK, Dave GS, Kothari RK. Biodegradable gelatin-ciprofloxacin-montmorillonite composite hydrogels for controlled drug release and wound dressing application. Colloids Surf B Biointerfaces 2014; 122:175-183. [PMID: 25033437 DOI: 10.1016/j.colsurfb.2014.06.051] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2014] [Revised: 06/21/2014] [Accepted: 06/23/2014] [Indexed: 02/04/2023]
Abstract
This work reports intercalation of a sparingly soluble antibiotic (ciprofloxacin) into layered nanostructure silicate, montmorillonite (MMT) and its reaction with bone derived polypeptide, gelatin that yields three-dimensional composite hydrogel. Drug intercalation results in changes in MMT layered space and drug loaded MMT and gelatin creates 3D morphology with biodegradable composite hydrogels. These changes can be correlated with electrostatic interactions between the drug, MMT and the gelatin polypeptides as confirmed by X-ray diffraction patterns, thermal, spectroscopic analyses, computational modeling and 3D morphology revealed by SEM and TEM analysis. No significant changes in structural and functional properties of drug was found after intercalation in MMT layers and composite hydrogels. In vitro drug release profiles showed controlled release up to 150h. The drug loaded composite hydrogels were tested on lung cancer cells (A549) by MTT assay. The results of in vitro cell migration and proliferation assay were promising as composite hydrogels induced wound healing progression. In vitro biodegradation was studied using proteolytic enzymes (lysozyme and protease K) at physiological conditions. This new approach of drug intercalation into the layered nanostructure silicate by ion-exchange may have significant applications in cost-effective wound dressing biomaterial with antimicrobial property.
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Affiliation(s)
- Bhavesh D Kevadiya
- Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute, Council of Scientific and Industrial Research (CSIR), Gijubhai Badheka Marg, Bhavnagar 364 021, Gujarat, India; Institute of Science, Nirma University, Ahmedabad 382 481, Gujarat, India
| | - Shalini Rajkumar
- Institute of Science, Nirma University, Ahmedabad 382 481, Gujarat, India.
| | - Hari C Bajaj
- Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute, Council of Scientific and Industrial Research (CSIR), Gijubhai Badheka Marg, Bhavnagar 364 021, Gujarat, India.
| | - Shiva Shankaran Chettiar
- Department of Biotechnology, Shree Ramkrishna Institute of Computer Education and Applied Sciences, Veer Narmad South Gujarat University, Surat, India.
| | - Kalpeshgiri Gosai
- Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute, Council of Scientific and Industrial Research (CSIR), Gijubhai Badheka Marg, Bhavnagar 364 021, Gujarat, India
| | - Harshad Brahmbhatt
- Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute, Council of Scientific and Industrial Research (CSIR), Gijubhai Badheka Marg, Bhavnagar 364 021, Gujarat, India
| | - Adarsh S Bhatt
- Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute, Council of Scientific and Industrial Research (CSIR), Gijubhai Badheka Marg, Bhavnagar 364 021, Gujarat, India
| | - Yogesh K Barvaliya
- Department of Biochemistry, Saurashtra University, Rajkot 360 005, Gujarat, India.
| | - Gaurav S Dave
- Department of Biochemistry, Saurashtra University, Rajkot 360 005, Gujarat, India
| | - Ramesh K Kothari
- Department of Microbiology, Christ College, Rajkot 360 005, Gujarat, India.
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50
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Salcedo I, Sandri G, Aguzzi C, Bonferoni C, Cerezo P, Sánchez-Espejo R, Viseras C. Intestinal permeability of oxytetracycline from chitosan-montmorillonite nanocomposites. Colloids Surf B Biointerfaces 2014; 117:441-8. [DOI: 10.1016/j.colsurfb.2013.11.009] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2013] [Revised: 10/31/2013] [Accepted: 11/07/2013] [Indexed: 11/28/2022]
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