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Priyanka, Abusalah MAH, Chopra H, Sharma A, Mustafa SA, Choudhary OP, Sharma M, Dhawan M, Khosla R, Loshali A, Sundriyal A, Saini J. Nanovaccines: A game changing approach in the fight against infectious diseases. Biomed Pharmacother 2023; 167:115597. [PMID: 37783148 DOI: 10.1016/j.biopha.2023.115597] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 09/24/2023] [Accepted: 09/25/2023] [Indexed: 10/04/2023] Open
Abstract
The field of nanotechnology has revolutionised global attempts to prevent, treat, and eradicate infectious diseases in the foreseen future. Nanovaccines have proven to be a valuable pawn in this novel technology. Nanovaccines are made up of nanoparticles that are associated with or prepared with components that can stimulate the host's immune system. In addition to their delivery capabilities, the nanocarriers have been demonstrated to possess intrinsic adjuvant properties, working as immune cell stimulators. Thus, nanovaccines have the potential to promote rapid as well as long-lasting humoral and cellular immunity. The nanovaccines have several possible benefits, including site-specific antigen delivery, increased antigen bioavailability, and a diminished adverse effect profile. To avail these benefits, several nanoparticle-based vaccines are being developed, including virus-like particles, liposomes, polymeric nanoparticles, nanogels, lipid nanoparticles, emulsion vaccines, exomes, and inorganic nanoparticles. Inspired by their distinctive properties, researchers are working on the development of nanovaccines for a variety of applications, such as cancer immunotherapy and infectious diseases. Although a few challenges still need to be overcome, such as modulation of the nanoparticle pharmacokinetics to avoid rapid elimination from the bloodstream by the reticuloendothelial system, The future prospects of this technology are also assuring, with multiple options such as personalised vaccines, needle-free formulations, and combination nanovaccines with several promising candidates.
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Affiliation(s)
- Priyanka
- Department of Veterinary Microbiology, College of Veterinary Science, Guru Angad Dev Veterinary and Animal Sciences University (GADVASU), Rampura Phul, Bathinda 151103, Punjab, India
| | - Mai Abdel Haleem Abusalah
- Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Zarqa University, Al-Zarqa 13132, Jordan
| | - Hitesh Chopra
- Department of Biosciences, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
| | - Abhilasha Sharma
- Department of Life Science, Gujarat University, University School of Sciences, Gujarat University, Ahmedabad 380009, Gujarat, India
| | - Suhad Asad Mustafa
- Scientific Research Center/ Salahaddin University-Erbil, Erbil, Kurdistan Region, Iraq
| | - Om Prakash Choudhary
- Department of Veterinary Anatomy, College of Veterinary Science, Guru Angad Dev Veterinary and Animal Sciences University (GADVASU), Rampura Phul, Bathinda 151103, Punjab, India.
| | - Manish Sharma
- University Institute of Biotechnology, Department of Biotechnology, Chandigarh University, Mohali 140413, Punjab, India
| | - Manish Dhawan
- Department of Microbiology, Punjab Agricultural University, Ludhiana 141004, Punjab, India; Trafford College, Altrincham, Manchester WA14 5PQ, UK.
| | - Rajiv Khosla
- Department of Biotechnology, Doaba College, Jalandhar 144004, Punjab, India
| | - Aanchal Loshali
- Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India
| | - Ankush Sundriyal
- School of Pharmaceutical Sciences and Research, Sardar Bhagwan Singh University, Balawala, Dehradun 248001, India
| | - Jyoti Saini
- Department of Veterinary Anatomy, College of Veterinary Science, Guru Angad Dev Veterinary and Animal Sciences University (GADVASU), Rampura Phul, Bathinda 151103, Punjab, India
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Heng WT, Yew JS, Poh CL. Nanovaccines against Viral Infectious Diseases. Pharmaceutics 2022; 14:2554. [PMID: 36559049 PMCID: PMC9784285 DOI: 10.3390/pharmaceutics14122554] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/17/2022] [Accepted: 11/18/2022] [Indexed: 11/23/2022] Open
Abstract
Infectious diseases have always been regarded as one of the greatest global threats for the last century. The current ongoing COVID-19 pandemic caused by SARS-CoV-2 is living proof that the world is still threatened by emerging infectious diseases. Morbidity and mortality rates of diseases caused by Coronavirus have inflicted devastating social and economic outcomes. Undoubtedly, vaccination is the most effective method of eradicating infections and infectious diseases that have been eradicated by vaccinations, including Smallpox and Polio. To date, next-generation vaccine candidates with novel platforms are being approved for emergency use, such as the mRNA and viral vectored vaccines against SARS-CoV-2. Nanoparticle based vaccines are the perfect candidates as they demonstrated targeted antigen delivery, improved antigen presentation, and sustained antigen release while providing self-adjuvanting functions to stimulate potent immune responses. In this review, we discussed most of the recent nanovaccines that have found success in immunization and challenge studies in animal models in comparison with their naked vaccine counterparts. Nanovaccines that are currently in clinical trials are also reviewed.
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Affiliation(s)
| | | | - Chit Laa Poh
- Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Subang Jaya 47500, Malaysia
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Rigi M, Ojagh SM, Alishahi A, Hasani S. Characterizing and Developing the Antioxidant and Antimicrobial Properties of the Nano-Encapsulated Bioactive Compounds of Spirulina platensis in Liposome. JOURNAL OF AQUATIC FOOD PRODUCT TECHNOLOGY 2022. [DOI: 10.1080/10498850.2022.2081951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Mahin Rigi
- Department of Fisheries, Faculty of Fisheries and the Environment, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran
| | - Seyed Mahdi Ojagh
- Department of Fisheries, Faculty of Fisheries and the Environment, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran
- Department of Seafood Processing, Faculty of Marine Sciences, Tarbiat Modares University, Noor, Iran
| | - Alireza Alishahi
- Department of Fisheries, Faculty of Fisheries and the Environment, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran
| | - Shirin Hasani
- Department of Fisheries, Faculty of Fisheries and the Environment, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran
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Loh FK, Nathan S, Chow SC, Fang CM. Vaccination challenges and strategies against long-lived Toxoplasma gondii. Vaccine 2019; 37:3989-4000. [PMID: 31186188 DOI: 10.1016/j.vaccine.2019.05.083] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Revised: 04/05/2019] [Accepted: 05/21/2019] [Indexed: 01/03/2023]
Abstract
Since the discovery of Toxoplasma gondii in 1908, it is estimated that one-third of the global population has been exposed to this ubiquitous intracellular protozoan. The complex life cycle of T. gondii has enabled itself to overcome stress and transmit easily within a broad host range thus achieving a high seroprevalence worldwide. To date, toxoplasmosis remains one of the most prevalent HIV-associated opportunistic central nervous system infections. This review presents a comprehensive overview of different vaccination approaches ranging from traditional inactivated whole-T. gondii vaccines to the popular DNA vaccines. Extensive discussions are made to highlight the challenges in constructing these vaccines, selecting adjuvants as well as delivery methods, immunisation approaches and developing study models. Herein we also deliberate over the latest and promising enhancement strategies that can address the limitations in developing an effective T. gondii prophylactic vaccine.
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Affiliation(s)
- Fei-Kean Loh
- Division of Biomedical Sciences, School of Pharmacy, The University of Nottingham Malaysia Campus, 43500 Semenyih, Selangor, Malaysia
| | - Sheila Nathan
- School of Biosciences and Biotechnology, Faculty of Science & Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia
| | - Sek-Chuen Chow
- School of Science, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor, Malaysia
| | - Chee-Mun Fang
- Division of Biomedical Sciences, School of Pharmacy, The University of Nottingham Malaysia Campus, 43500 Semenyih, Selangor, Malaysia.
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Polymeric Nanoparticles in Gene Therapy: New Avenues of Design and Optimization for Delivery Applications. Polymers (Basel) 2019; 11:polym11040745. [PMID: 31027272 PMCID: PMC6523186 DOI: 10.3390/polym11040745] [Citation(s) in RCA: 181] [Impact Index Per Article: 30.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 04/08/2019] [Accepted: 04/18/2019] [Indexed: 01/19/2023] Open
Abstract
The field of polymeric nanoparticles is quickly expanding and playing a pivotal role in a wide spectrum of areas ranging from electronics, photonics, conducting materials, and sensors to medicine, pollution control, and environmental technology. Among the applications of polymers in medicine, gene therapy has emerged as one of the most advanced, with the capability to tackle disorders from the modern era. However, there are several barriers associated with the delivery of genes in the living system that need to be mitigated by polymer engineering. One of the most crucial challenges is the effectiveness of the delivery vehicle or vector. In last few decades, non-viral delivery systems have gained attention because of their low toxicity, potential for targeted delivery, long-term stability, lack of immunogenicity, and relatively low production cost. In 1987, Felgner et al. used the cationic lipid based non-viral gene delivery system for the very first time. This breakthrough opened the opportunity for other non-viral vectors, such as polymers. Cationic polymers have emerged as promising candidates for non-viral gene delivery systems because of their facile synthesis and flexible properties. These polymers can be conjugated with genetic material via electrostatic attraction at physiological pH, thereby facilitating gene delivery. Many factors influence the gene transfection efficiency of cationic polymers, including their structure, molecular weight, and surface charge. Outstanding representatives of polymers that have emerged over the last decade to be used in gene therapy are synthetic polymers such as poly(l-lysine), poly(l-ornithine), linear and branched polyethyleneimine, diethylaminoethyl-dextran, poly(amidoamine) dendrimers, and poly(dimethylaminoethyl methacrylate). Natural polymers, such as chitosan, dextran, gelatin, pullulan, and synthetic analogs, with sophisticated features like guanidinylated bio-reducible polymers were also explored. This review outlines the introduction of polymers in medicine, discusses the methods of polymer synthesis, addressing top down and bottom up techniques. Evaluation of functionalization strategies for therapeutic and formulation stability are also highlighted. The overview of the properties, challenges, and functionalization approaches and, finally, the applications of the polymeric delivery systems in gene therapy marks this review as a unique one-stop summary of developments in this field.
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Farris E, Sanderfer K, Lampe A, Brown DM, Ramer-Tait AE, Pannier AK. Oral Non-Viral Gene Delivery for Applications in DNA Vaccination and Gene Therapy. CURRENT OPINION IN BIOMEDICAL ENGINEERING 2018; 7:51-57. [PMID: 31011691 PMCID: PMC6474414 DOI: 10.1016/j.cobme.2018.09.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Non-viral gene delivery via the oral route is a promising strategy for improving outcomes of DNA vaccination and gene therapy applications. Unlike traditional parenteral administration routes, the oral route is a non-invasive approach that lends itself to high patient compliance and ease of dosing. Moreover, oral administration allows for both local and systemic production of therapeutic genes or, in the case of DNA vaccination, mucosal and systemic immunity. However, the oral route presents distinct challenges and barriers to achieving successful gene delivery. Oral non-viral gene delivery systems must be able to survive the harsh and variable environments (e.g. acidic pH, degrading enzymes, mucus layer) encountered during transit through the gastrointestinal tract, while still allowing for efficient transgene production at sites of interest. These barriers present unique design challenges for researchers in material selection and in improving the transfection efficiency of orally delivered genes. This review provides an overview of advancements in the design of oral non-viral gene delivery systems, and highlights recent and important developments towards improving orally delivered genes for applications in gene therapy and DNA vaccination.
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Affiliation(s)
- Eric Farris
- Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, NE 68583
| | - Kari Sanderfer
- Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, NE 68583
| | - Anna Lampe
- School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583
- Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583
| | - Deborah M Brown
- School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583
- Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583
| | - Amanda E Ramer-Tait
- Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE 68588
| | - Angela K Pannier
- Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, NE 68583
- Nebraska Center for Materials and Nanoscience, University of Nebraska-Lincoln, Lincoln, NE 68588
- Center for Nanohybrid Functional Materials, University of Nebraska-Lincoln, Lincoln, NE 68588
- Mary and Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE 68198
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Farris E, Brown DM, Ramer-Tait AE, Pannier AK. Chitosan-zein nano-in-microparticles capable of mediating in vivo transgene expression following oral delivery. J Control Release 2017; 249:150-161. [PMID: 28153762 DOI: 10.1016/j.jconrel.2017.01.035] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Accepted: 01/26/2017] [Indexed: 12/16/2022]
Abstract
The oral route is an attractive delivery route for the administration of DNA-based therapeutics, specifically for applications in gene therapy and DNA vaccination. However, oral DNA delivery is complicated by the harsh and variable conditions encountered throughout gastrointestinal (GI) transit, leading to degradation of the delivery vector and DNA cargo, and subsequent inefficient delivery to target cells. In this work, we demonstrate the development and optimization of a hybrid-dual particulate delivery system consisting of two natural biomaterials, zein (ZN) and chitosan (CS), to mediate oral DNA delivery. Chitosan-Zein Nano-in-Microparticles (CS-ZN-NIMs), consisting of core Chitosan/DNA nanoparticles (CS/DNA NPs) prepared by ionic gelation with sodium tripolyphosphate (TPP), further encapsulated in ZN microparticles, were formulated using a water-in-oil emulsion (W/O). The resulting particles exhibited high CS/DNA NP loading and encapsulation within ZN microparticles. DNA release profiles in simulated gastric fluid (SGF) were improved compared to un-encapsulated CS/DNA NPs. Further, site-specific degradation of the outer ZN matrix and release of transfection competent CS/DNA NPs occurred in simulated intestinal conditions with CS/DNA NP cores successfully mediating transfection in vitro. Finally, CS-ZN-NIMs encoding GFP delivered by oral gavage in vivo induced the production of anti-GFP IgA antibodies, demonstrating in vivo transfection and expression. Together, these results demonstrate the successful formulation of CS-ZN-NIMs and their potential to improve oral gene delivery through improved protection and controlled release of DNA cargo.
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Affiliation(s)
- Eric Farris
- Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, NE 68583, United States
| | - Deborah M Brown
- School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, United States; Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, United States
| | - Amanda E Ramer-Tait
- Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE 68588, United States
| | - Angela K Pannier
- Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, NE 68583, United States; Nebraska Center for Materials and Nanoscience, University of Nebraska-Lincoln, Lincoln, NE 68588, United States; Center for Nanohybrid Functional Materials, University of Nebraska-Lincoln, Lincoln, NE 68588, United States; Mary and Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE 68198, United States.
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Farris E, Brown DM, Ramer-Tait AE, Pannier AK. Micro- and nanoparticulates for DNA vaccine delivery. Exp Biol Med (Maywood) 2016; 241:919-29. [PMID: 27048557 PMCID: PMC4950349 DOI: 10.1177/1535370216643771] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
DNA vaccination has emerged as a promising alternative to traditional protein-based vaccines for the induction of protective immune responses. DNA vaccines offer several advantages over traditional vaccines, including increased stability, rapid and inexpensive production, and flexibility to produce vaccines for a wide variety of infectious diseases. However, the immunogenicity of DNA vaccines delivered as naked plasmid DNA is often weak due to degradation of the DNA by nucleases and inefficient delivery to immune cells. Therefore, biomaterial-based delivery systems based on micro- and nanoparticles that encapsulate plasmid DNA represent the most promising strategy for DNA vaccine delivery. Microparticulate delivery systems allow for passive targeting to antigen presenting cells through size exclusion and can allow for sustained presentation of DNA to cells through degradation and release of encapsulated vaccines. In contrast, nanoparticle encapsulation leads to increased internalization, overall greater transfection efficiency, and the ability to increase uptake across mucosal surfaces. Moreover, selection of the appropriate biomaterial can lead to increased immune stimulation and activation through triggering innate immune response receptors and target DNA to professional antigen presenting cells. Finally, the selection of materials with the appropriate properties to achieve efficient delivery through administration routes conducive to high patient compliance and capable of generating systemic and local (i.e. mucosal) immunity can lead to more effective humoral and cellular protective immune responses. In this review, we discuss the development of novel biomaterial-based delivery systems to enhance the delivery of DNA vaccines through various routes of administration and their implications for generating immune responses.
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Affiliation(s)
- Eric Farris
- Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
| | - Deborah M Brown
- School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE 68588, USA Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
| | - Amanda E Ramer-Tait
- Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
| | - Angela K Pannier
- Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA Nebraska Center for Materials and Nanoscience, University of Nebraska-Lincoln, Lincoln, NE 68588, USA Center for Nanohybrid Functional Materials, University of Nebraska-Lincoln, Lincoln, NE 68588, USA Mary and Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE 68198, USA
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Zhang W, Wang J, Zhang C, Fang Q, Shu J, Li S, Jin J, Wang D, Nie Z, Lv Z, Zhang Y. Synergetic Protein Factors That Improve rhGM-CSF Absorption via an Oral Route Exist in Silkworm Pupae. Mol Pharm 2015; 12:1347-55. [PMID: 25775407 DOI: 10.1021/mp500371g] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Recent studies have demonstrated that recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) produced by the silkworm pupae bioreactor is absorbed into blood through oral administration and functions as an active cytokine. The aim of this study was to further examine and identify synergetic protein factors in silkworm pupae that improve rhGM-CSF absorption via an oral route. The concentrations of rhGM-CSF in serum were evaluated in mice after oral administration of rhGM-CSF using different chemical compositions of silkworm pupae as pharmaceutical excipients. The experimental data revealed that the supernatant lyophilized powder (SLP) of a homogenized slurry of silkworm pupae caused a significant increase in the rhGM-CSF level in blood when rhGM-CSF was orally administered with SLP, suggesting that synergetic protein factors that improve the oral absorption of rhGM-CSF primarily exist in SLP. As shown by scanning electron microscopy, microspheres were formed when rhGM-CSF was coated with SLP. Animal experimental data showed that the absorption of orally administered rhGM-CSF through the gastrointestinal (GI) tract primarily resulted from protein factors present in the SLP retentate obtained after 10 kDa ultrafiltration. Surface plasmon resonance spectroscopy analysis demonstrated that several protein factors present in the SLP retentate obtained after 10 kDa ultrafiltration were bound to rhGM-CSF. Proteins bound to rhGM-CSF by liquid chromatography-mass spectrometry were identified as chymotrypsin inhibitor SCI-II precursor, cationic peptide CP8 precursor, Kazal-type proteinase inhibitor, and chymotrypsin inhibitor SCI-I. These findings indicate that these proteinase inhibitors play an important role in improving rhGM-CSF absorption in the GI tract.
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Affiliation(s)
- Wenping Zhang
- Institute of Biochemistry, College of Life Science, Zhejiang Sci-Tech University, Hangzhou 310018, China
| | - Jian Wang
- Institute of Biochemistry, College of Life Science, Zhejiang Sci-Tech University, Hangzhou 310018, China
| | - Chen Zhang
- Institute of Biochemistry, College of Life Science, Zhejiang Sci-Tech University, Hangzhou 310018, China
| | - Qiang Fang
- Institute of Biochemistry, College of Life Science, Zhejiang Sci-Tech University, Hangzhou 310018, China
| | - Jianhong Shu
- Institute of Biochemistry, College of Life Science, Zhejiang Sci-Tech University, Hangzhou 310018, China
| | - Si Li
- Institute of Biochemistry, College of Life Science, Zhejiang Sci-Tech University, Hangzhou 310018, China
| | - Jia Jin
- Institute of Biochemistry, College of Life Science, Zhejiang Sci-Tech University, Hangzhou 310018, China
| | - Dan Wang
- Institute of Biochemistry, College of Life Science, Zhejiang Sci-Tech University, Hangzhou 310018, China
| | - Zuoming Nie
- Institute of Biochemistry, College of Life Science, Zhejiang Sci-Tech University, Hangzhou 310018, China
| | - Zhengbing Lv
- Institute of Biochemistry, College of Life Science, Zhejiang Sci-Tech University, Hangzhou 310018, China
| | - Yaozhou Zhang
- Institute of Biochemistry, College of Life Science, Zhejiang Sci-Tech University, Hangzhou 310018, China
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Agrawal U, Sharma R, Gupta M, Vyas SP. Is nanotechnology a boon for oral drug delivery? Drug Discov Today 2014; 19:1530-46. [PMID: 24786464 DOI: 10.1016/j.drudis.2014.04.011] [Citation(s) in RCA: 86] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2014] [Revised: 03/12/2014] [Accepted: 04/22/2014] [Indexed: 12/14/2022]
Abstract
The oral route for drug delivery is regarded as the optimal route for achieving therapeutic benefits owing to increased patient compliance. Despite phenomenal advances in injectable, transdermal, nasal and other routes of administration, the reality is that oral drug delivery remains well ahead of the pack as the preferred delivery route. Nanocarriers can overcome the major challenges associated with this route of administration: mainly poor solubility, stability and biocompatibility of drugs. This review focuses on the potential of various polymeric drug delivery systems in oral administration, their pharmacokinetics, in vitro and in vivo models, toxicity and regulatory aspects.
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Affiliation(s)
- Udita Agrawal
- Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr H.S. Gour Vishwavidyalaya, Sagar, MP 470003, India
| | - Rajeev Sharma
- Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr H.S. Gour Vishwavidyalaya, Sagar, MP 470003, India
| | - Madhu Gupta
- Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr H.S. Gour Vishwavidyalaya, Sagar, MP 470003, India
| | - Suresh P Vyas
- Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr H.S. Gour Vishwavidyalaya, Sagar, MP 470003, India.
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Bhatt P, Khatri N, Kumar M, Baradia D, Misra A. Microbeads mediated oral plasmid DNA delivery using polymethacrylate vectors: an effectual groundwork for colorectal cancer. Drug Deliv 2014; 22:849-61. [DOI: 10.3109/10717544.2014.898348] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Hanafi A, Nograles N, Abdullah S, Shamsudin MN, Rosli R. Cellulose Acetate Phthalate Microencapsulation and Delivery of Plasmid DNA to the Intestines. J Pharm Sci 2013. [DOI: 10.1002/jps.23389] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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Regier MC, Taylor JD, Borcyk T, Yang Y, Pannier AK. Fabrication and characterization of DNA-loaded zein nanospheres. J Nanobiotechnology 2012. [PMID: 23199119 PMCID: PMC3524772 DOI: 10.1186/1477-3155-10-44] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Background Particulates incorporating DNA are promising vehicles for gene delivery, with the ability to protect DNA and provide for controlled, localized, and sustained release and transfection. Zein, a hydrophobic protein from corn, is biocompatible and has properties that make it a promising candidate material for particulate delivery, including its ability to form nanospheres through coacervation and its insolubility under physiological conditions, making it capable of sustained release of encapsulated compounds. Due to the promise of this natural biomaterial for drug delivery, the objective of this study was to formulate zein nanospheres encapsulating DNA as the therapeutic compound, and to characterize size, charge, sustained release, cell cytotoxicity and cellular internalization of these particles. Results Zein nanospheres encapsulating DNA were fabricated using a coacervation technique, without the use of harsh solvents or temperatures, resulting in the preservation of DNA integrity and particles with diameters that ranged from 157.8 ± 3.9 nm to 396.8 ± 16.1 nm, depending on zein to DNA ratio. DNA encapsulation efficiencies were maximized to 65.3 ± 1.9% with a maximum loading of 6.1 ± 0.2 mg DNA/g zein. The spheres protected encapsulated DNA from DNase I degradation and exhibited sustained plasmid release for at least 7 days, with minimal burst during the initial phase of release. Zein/DNA nanospheres demonstrated robust biocompatibility, cellular association, and internalization. Conclusions This study represents the first report on the formation of zein particles encapsulating plasmid DNA, using simple fabrication techniques resulting in preservation of plasmid integrity and tunable sizes. DNA encapsulation efficiencies were maximized to acceptable levels at higher zein to DNA ratios, while loading was comparable to that of other hydrophilic compounds encapsulated in zein and that of DNA incorporated into PLGA nano- and microspheres. The hydrophobic nature of zein resulted in spheres capable of sustained release of plasmid DNA. Zein particles may be an excellent potential tool for the delivery of DNA with the ability to be fine-tuned for specific applications including oral gene delivery, intramuscular delivery, and in the fabrication of tissue engineering scaffolds.
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Affiliation(s)
- Mary C Regier
- Department of Biological Systems Engineering, University of Nebraska-Lincoln, 231 Chase Hall, Lincoln, NE 68583-0726, USA
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Mechanistic studies on the uptake and intracellular trafficking of novel cyclodextrin transfection complexes by intestinal epithelial cells. Int J Pharm 2011; 413:174-83. [DOI: 10.1016/j.ijpharm.2011.04.021] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2011] [Revised: 04/06/2011] [Accepted: 04/08/2011] [Indexed: 11/18/2022]
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Channarong S, Chaicumpa W, Sinchaipanid N, Mitrevej A. Development and evaluation of chitosan-coated liposomes for oral DNA vaccine: the improvement of Peyer's patch targeting using a polyplex-loaded liposomes. AAPS PharmSciTech 2011; 12:192-200. [PMID: 21194014 DOI: 10.1208/s12249-010-9559-9] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2010] [Accepted: 11/30/2010] [Indexed: 11/30/2022] Open
Abstract
The aim of this study was to develop chitosan-coated and polyplex-loaded liposomes (PLLs) containing DNA vaccine for Peyer's patch targeting. Plain liposomes carrying plasmid pRc/CMV-HBs were prepared by the reverse-phase evaporation method. Chitosan coating was carried out by incubation of the liposomal suspensions with chitosan solution. Main lipid components of liposomes were phosphatidylcholine/cholesterol. Sodium deoxycholate and dicetyl phosphate were used as negative charge inducers. The zeta potentials of plain liposomes were strongly affected by the pH of the medium. Coating with chitosan variably increased the surface charges of the liposomes. To increase the zeta potential and stability of the liposome, chitosan was also used as a DNA condensing agent to form a polyplex. The PLLs were coated with chitosan solution. In vivo study of PLLs was carried out in comparison with chitosan-coated liposomes using plasmid encoding green fluorescence protein as a reporter. A single dose of plasmid equal to 100 μg was intragastrically inoculated into BALB/c mice. The expression of green fluorescence protein (GFP) was detected after 24 h using a confocal laser scanning microscope. The signal of GFP was obtained from positively charged chitosan-coated liposomes but found only at the upper part of duodenum. With chitosan-coated PLL540, the signal of GFP was found throughout the intestine. Chitosan-coated PLL demonstrated a higher potential to deliver the DNA to the distal intestine than the chitosan-coated liposomes due to the increase in permanent positive surface charges and the decreased enzymatic degradation.
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O'Neill MJ, Bourre L, Melgar S, O'Driscoll CM. Intestinal delivery of non-viral gene therapeutics: physiological barriers and preclinical models. Drug Discov Today 2011; 16:203-18. [PMID: 21262379 DOI: 10.1016/j.drudis.2011.01.003] [Citation(s) in RCA: 86] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2010] [Revised: 10/18/2010] [Accepted: 01/14/2011] [Indexed: 01/12/2023]
Abstract
The future of nucleic acid-based therapeutics is dependent on achieving successful delivery. Recently, there has been an increasing interest in delivery via the gastrointestinal tract. Gene therapy via this route has many advantages, including non-invasive access and the versatility to treat local diseases, such as inflammatory bowel disease, as well as systemic diseases, such as haemophilia. However, the intestine presents several distinct barriers and, therefore, the design of robust non-viral delivery systems is key to future success. Several non-viral delivery strategies have provided evidence of activity in vivo. To facilitate the design of more efficient and safe gene medicines, more physiologically relevant models, at both the in vitro and in vivo levels, are essential.
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Affiliation(s)
- Martin J O'Neill
- Pharmacodelivery Group, School of Pharmacy, University College Cork, Ireland
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Jain AK, Goyal AK, Mishra N, Vaidya B, Mangal S, Vyas SP. PEG–PLA–PEG block copolymeric nanoparticles for oral immunization against hepatitis B. Int J Pharm 2010; 387:253-62. [DOI: 10.1016/j.ijpharm.2009.12.013] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2009] [Revised: 12/03/2009] [Accepted: 12/04/2009] [Indexed: 10/20/2022]
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Arulmuthu ER, Williams DJ, Versteeg HK. The arrival of genetic engineering. ACTA ACUST UNITED AC 2009; 28:40-54. [PMID: 19150770 DOI: 10.1109/memb.2008.931015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Eugene R Arulmuthu
- Healthcare Engineering Group, Wolfson School of Mechanical and Manufacturing Engineering, Loughborough University, Loughborough LE11 3TU, UK
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20
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Kochetkova SV, Fillipova EA, Kolganova NA, Timofeev EN, Florent'ev VL. [Oligonucleotide analogues bearing an acyclonucleoside linked by an internucleotide amide bond]. RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY 2008; 34:227-35. [PMID: 18522279 DOI: 10.1134/s1068162008020106] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Oligonucleotide analogues bearing an acyclocytidine linked to thymidine by an amide (3'-O-CH2-CO-N-5') bond were synthesized. Melting curves of duplexes formed by modified oligonucleotides and complementary natural oligomers were obtained and thermodynamic parameters of their formation were measured. Replacement of dCpT by a modified dinucleotide only moderately decreased the melting temperature of these modified duplexes in comparison with unmodified duplexes containing complementary natural bases. CD spectra of modified duplexes were studied, and the duplex spatial structures are discussed. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2008, vol. 34, no. 2; see also http://www.maik.ru.
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21
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Celec P, Kukucková M, Renczésová V, Natarajan S, Pálffy R, Gardlík R, Hodosy J, Behuliak M, Vlková B, Minárik G, Szemes T, Stuchlík S, Turna J. Biological and biomedical aspects of genetically modified food. Biomed Pharmacother 2005; 59:531-40. [PMID: 16298508 DOI: 10.1016/j.biopha.2005.07.013] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2005] [Accepted: 07/05/2005] [Indexed: 11/23/2022] Open
Abstract
Genetically modified (GM) foods are the product of one of the most progressive fields of science-biotechnology. There are major concerns about GM foods in the public; some of them are reasonable, some of them are not. Biomedical risks of GM foods include problems regarding the potential allergenicity, horizontal gene transfer, but environmental side effects on biodiversity must also be recognized. Numerous methods have been developed to assess the potential risk of every GM food type. Benefits of the first generation of GM foods were oriented towards the production process and companies, the second generation of GM foods offers, on contrary, various advantages and added value for the consumer. This includes improved nutritional composition or even therapeutic effects. Recombinant probiotics and the principle of alternative gene therapy represent the latest approach of using GM organisms for biomedical applications. This article tries to summarize and to explain the problematic topic of GM food.
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Affiliation(s)
- Peter Celec
- Biomed Research and Publishing Group, Bratislava, Slovakia.
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Pálffy R, Gardlík R, Hodosy J, Behuliak M, Resko P, Radvánský J, Celec P. Bacteria in gene therapy: bactofection versus alternative gene therapy. Gene Ther 2005; 13:101-5. [PMID: 16163379 DOI: 10.1038/sj.gt.3302635] [Citation(s) in RCA: 76] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Recent advances in gene therapy can be attributed to improvements of gene delivery vectors. New viral and nonviral transport vehicles that considerably increase the efficiency of transfection have been prepared. However, these vectors still have many disadvantages that are difficult to overcome, thus, a new approach is needed. The approach of bacterial delivery could in the future be important for gene therapy applications. In this article we try to summarize the most important modifications that are used for the preparation of applied strains, difficulties that are related with bacterial gene delivery and the current use of bactofection in animal experiments and clinical trials. Important differences to the alternative gene therapy (AGT) are discussed. AGT resembles bacteria-mediated protein delivery, as the therapeutical proteins are produced not by host cells but by the bacteria in situ and the expression can be regulated exogenously. Although the procedure of bacterial gene delivery is far from being definitely solved, bactofection remains a promising technique for transfection in human gene therapy.
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Affiliation(s)
- R Pálffy
- BiomeD Research and Publishing Group, Faculty of Natural Sciences, Comenius University, Bratislava, Slovak Republic.
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Chen J, Yang WL, Li G, Qian J, Xue JL, Fu SK, Lu DR. Transfection of mEpo gene to intestinal epithelium in vivo mediated by oral delivery of chitosan-DNA nanoparticles. World J Gastroenterol 2004; 10:112-6. [PMID: 14695780 PMCID: PMC4717060 DOI: 10.3748/wjg.v10.i1.112] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To prepare the chitosan-pmEpo nanoparticles and to study their ability for transcellular and paracellular transport across intestinal epithelia by oral administration.
METHODS: ICR mice were fed with recombinant plasmid AAV-tetO-CMV-mEpo (containing mEpo gene) or pCMVβ (containing LacZ gene), whether it was wrapped by chitosan or no. Its size and shape were observed by transmission electron microscopy. Agarose gel electrophoresis was used to assess the efficiency of encapsulation and stability against nuclease digestion. Before and after oral treatmant, blood samples were collected by retro-orbital puncture, and hematocrits were used to show the physiological effect of mEpo.
RESULTS: Chitosan was able to successfully wrap the plasmid and to protect it from DNase degradation. Transmission electron microscopy showed that freshly prepared particles were approximately 70-150 nm in size and fairly spherical. Three days after fed the chitosan-pCMVβ complex was fed, the mice were killed and most of the stomach and 30% of the small intestine were stained. Hematocrit was not modified in naive and ‘naked’ mEpo-fed mice, a rapid increase of hematocrit was observed during the first 4 days of treatment in chitosan-mEpo-fed animals, reaching 60.9 ± 1.2% (P < 0.01), and sustained for a week. The second feed (6 days after the first feed) was still able to promote a second hematocrit increase in chitosan-mEpo-fed animals, reaching 65.9 ± 1.4% (P < 0.01), while the second hematocrit increase did not appear in the ‘naked’ mEpo-second-fed mice.
CONCLUSION: Oral chitosan-DNA nanoparticles can efficiently deliver genes to enterocytes, and may be used as a useful tool for gene transfer.
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Affiliation(s)
- Jing Chen
- State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, China
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Abstract
Delivery of pharmaceuticals, particularly biotechnology products such as proteins, peptides, genes, oligonucleotides and vaccines, via the oral route remains problematic to this day. Instability in the gastrointestinal environment and poor permeability across the intestinal epithelial cell barrier contribute to poor oral bioavailability for many of these compounds. Current targeting strategies to overcome these issues are focused on three-part systems in which the drug (i) is loaded into a protective particulate carrier (ii) which is coated with target-specific ligands (iii) which mediate site-specific delivery of the drug-carrier complex. Protection from gastrointestinal degradative processes combined with site-specific delivery to absorptive regions of the intestinal tract is purported to yield high local concentrations of the drug of choice in close proximity with the epithelial cell layer and hence, transport across that barrier through a variety of mechanisms. This review examines the impact of cutting-edge technologies such as genomics and combinatorial chemistry on targeted oral drug delivery strategies. The explosion in rate of identification of new targets using genomics, together with high-throughput screening for target-specific ligands using combinatorial chemistry and phage display, has the potential to revolutionise this field. Particular reference is made to advances associated with targeted delivery of vaccines to M-cells or antigen-presenting cells in gut-associated lymphoid tissues.
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Affiliation(s)
- Imelda Lambkin
- Elan Biotechnology Research, Biotechnology Building, Trinity College, Dublin 2, Ireland
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Florence AT, Hussain N. Transcytosis of nanoparticle and dendrimer delivery systems: evolving vistas. Adv Drug Deliv Rev 2001; 50 Suppl 1:S69-89. [PMID: 11576696 DOI: 10.1016/s0169-409x(01)00184-3] [Citation(s) in RCA: 228] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
The translocation of particulate matter across the gastrointestinal tract is now a well documented phenomenon offering new potential for the delivery of drugs with poor dissolution profiles and labile chemistries via encapsulation in biodegradable nanoparticles. The last few years have seen an acceleration in the number of publications describing the varying facets of this approach and the multidisciplinary nature of this field. This review delineates data from this rather fragmented area and from cognate fields to provide a physicochemical viewpoint of the importance of surface chemistries of oral drug delivery vehicles and their interactions in and with gut contents prior to uptake. The role of lymphoid and non-lymphoid tissues is examined, and the role of bioadhesion is discussed. The exciting potential of molecular encapsulation of drugs via dendrimers and star branched molecules is discussed in the context of nanotechnological applications for the oral route. Evolving vistas include a better understanding of the plasticity of the intestinal epithelium and M-cell induction as well as the influence of disease states on particulate uptake. In this review we address a number of issues deemed vital to an understanding of the subject including (i) some background knowledge on particulate uptake (the subject of several reviews), (ii) factors affecting uptake such as diameter and surface charge and character, (iii) the dynamic nature of particle interactions in the gut, (iv) the dynamic nature of the processes of capture, adhesion, uptake, transcytosis and translocation, and (v) the influence of surface ligands.
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Affiliation(s)
- A T Florence
- Centre for Drug Delivery Research, The School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK.
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Abstract
Drug delivery has metamorphosed from the concept of a pill to molecular medicine in the past 100 years. Better appreciation and integration of pharmacokinetic and pharmacodynamic principles in design of drug delivery systems has led to improved therapeutic efficacy. A greater understanding of the molecular transport in relation to physico-chemical properties has led to the evolution of a biopharmaceutics classification system, which should be a future road map, governing drug design, development and delivery. While drugs belonging to class I and II will be delivered by established platform technologies, novel delivery strategies will evolve and mature to realize the potential of 'new generation' biotech and non biotech drugs belonging to class III and IV, respectively.
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Affiliation(s)
- O Pillai
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Sector 67, Ph X, - SAS Nagar -- 160 062 (Punjab), India
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