Peptide/protein vaccine delivery system based on PLGA particles.

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Abstract

Due to the excellent safety profile of poly (D,L-lactide-co-glycolide) (PLGA) particles in human, and their biodegradability, many studies have focused on the application of PLGA particles as a controlled-release vaccine delivery system. Antigenic proteins/peptides can be encapsulated into or adsorbed to the surface of PLGA particles. The gradual release of loaded antigens from PLGA particles is necessary for the induction of efficient immunity. Various factors can influence protein release rates from PLGA particles, which can be defined intrinsic features of the polymer, particle characteristics as well as protein and environmental related factors. The use of PLGA particles encapsulating antigens of different diseases such as hepatitis B, tuberculosis, chlamydia, malaria, leishmania, toxoplasma and allergy antigens will be described herein. The co-delivery of antigens and immunostimulants (IS) with PLGA particles can prevent the systemic adverse effects of immunopotentiators and activate both dendritic cells (DCs) and natural killer (NKs) cells, consequently enhancing the therapeutic efficacy of antigen-loaded PLGA particles. We will review co-delivery of different TLR ligands with antigens in various models, highlighting the specific strengths and weaknesses of the system. Strategies to enhance the immunotherapeutic effect of DC-based vaccine using PLGA particles can be designed to target DCs by functionalized PLGA particle encapsulating siRNAs of suppressive gene, and disease specific antigens. Finally, specific examples of cellular targeting where decorating the surface of PLGA particles target orally administrated vaccine to M-cells will be highlighted.

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Terminology for biorelated polymers and applications (IUPAC Recommendations 2012)

Michel Vert, Yoshiharu Doi, Karl-Heinz Hellwich … (2012)

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The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems--a review.

Susanne Fredenberg, Marie Wahlgren, Mats Reslow … (2011)

Poly(D,L-lactic-co-glycolic acid) (PLGA) is the most frequently used biodegradable polymer in the controlled release of encapsulated drugs. Understanding the release mechanisms, as well as which factors that affect drug release, is important in order to be able to modify drug release. Drug release from PLGA-based drug delivery systems is however complex. This review focuses on release mechanisms, and provides a survey and analysis of the processes determining the release rate, which may be helpful in elucidating this complex picture. The term release mechanism and the various techniques that have been used to study release mechanisms are discussed. The physico-chemical processes that influence the rate of drug release and the various mechanisms of drug release that have been reported in the literature are analyzed in this review, and practical examples are given. The complexity of drug release from PLGA-based drug delivery systems can make the generalization of results and predictions of drug release difficult. However, this complexity also provides many possible ways of solving problems and modifying drug release. Basic, generally applicable and mechanistic research provides pieces of the puzzle, which is useful in the development of controlled-release pharmaceuticals. Copyright © 2011 Elsevier B.V. All rights reserved.

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Nano/micro technologies for delivering macromolecular therapeutics using poly(D,L-lactide-co-glycolide) and its derivatives.

Raghavendra Mundargi, V Ramesh Babu, Vidhya Rangaswamy … (2008)

Biodegradable nano/microparticles of poly(D,L-lactide-co-glycolide) (PLGA) and PLGA-based polymers are widely explored as carriers for controlled delivery of macromolecular therapeutics such as proteins, peptides, vaccines, genes, antigens, growth factors, etc. These devices are mainly produced by emulsion or double-emulsion technique followed by solvent evaporation or spray drying. Drug encapsulation, particle size, additives added during formulation, molecular weight, ratio of lactide to glycolide moieties in PLGA and surface morphology could influence the release characteristics. Encapsulation efficiency and release rates through nano/microparticle-mediated drug delivery devices can be optimized to improve their therapeutic efficacy. In this review, important findings of the past decade on the encapsulation and release profiles of macromolecular therapeutics from PLGA and PLGA-based nano/microparticles are discussed critically in relation to nature and type of bioactive molecule, carrier polymer and experimental variables that influence the delivery of macromolecular therapeutics. Even though extensive research on biodegradable microparticles containing macromolecular drugs has greatly advanced to the level of production know-how, the effects of critical parameters influencing drug encapsulation are not sufficiently investigated for nano-scaled carriers. The present review attempts to address some important data on nano/microparticle-based delivery systems of PLGA and PLGA-derived polymers with reference to macromolecular drugs.