Self‐Healing Microencapsulation of Biomacromolecules without Organic Solvents

Reinhold, Samuel E.; Desai, Kashappa Goud H.; Zhang, Li; Olsen, Karl; Schwendeman, Steven P.

doi:10.1002/anie.201206387

Cited by 79 publications

(101 citation statements)

References 22 publications

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“…Yet, one of the major drawbacks for the PLGA particle system has been the potential exposure of antigens to harsh organic solvents since conventional technique for loading antigens into PLGA particles involves formation of single or double emulsion (O/W or W/O/W) and solvent evaporation. However, with the recent advances in micro-encapsulation of biomolecules into pre-formed, self-healing PLGA particles, antigens can be loaded into PLGA vaccine particles in aqueous condition with minimal loss of their integrity and antigenicity (99,100). …”

Section: Synthetic Polymer-based Particlesmentioning

confidence: 99%

Biomaterials for Nanoparticle Vaccine Delivery Systems

2014

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Subunit vaccination benefits from improved safety over attenuated or inactivated vaccines, but their limited capability to elicit long-lasting, concerted cellular and humoral immune responses is a major challenge. Recent studies have demonstrated that antigen delivery via nanoparticle formulations significantly improve immunogenicity of vaccines due to either intrinsic immunostimulatory properties of the materials or by co-entrapment of molecular adjuvants such as Toll-like receptor agonists. These studies have collectively shown that nanoparticles designed to mimic biophysical and biochemical cues of pathogens offer new exciting opportunities to enhance activation of innate immunity and elicit potent cellular and humoral immunity with minimal cytotoxicity. In this review, we present key research advances that were made within the last 5 years in the field of nanoparticle vaccine delivery systems. In particular, we focus on the impact of biomaterials composition, size, and surface charge of nanoparticles on modulation of particle biodistribution, delivery of antigens and immunostimulatory molecules, trafficking and targeting of antigen presenting cells, and overall immune responses in systemic and mucosal tissues. This review describes recent progresses in the design of nanoparticle vaccine delivery carriers, including liposomes, lipid-based particles, micelles and nanostructures composed of natural or synthetic polymers, and lipid-polymer hybrid nanoparticles.

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Section: Synthetic Polymer-based Particlesmentioning

confidence: 99%

Biomaterials for Nanoparticle Vaccine Delivery Systems

2014

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“…The alternative to anhydrous encapsulation, which does not require micronization and organic solvents, is to remotely load the protein in preformed microspheres in water. This process has shown improvement in stability of lysozyme and tetanus toxoid [46,97,98] and is described below in Section 3.3.…”

Section: Approaches To Overcome Issues Impeding Depot Developmentmentioning

confidence: 99%

Injectable controlled release depots for large molecules

Schwendeman

Shah

Bailey

et al. 2014

Journal of Controlled Release

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164

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Biodegradable, injectable depot formulations for long-term controlled drug release have improved therapy for a number of drug molecules and led to over a dozen highly successful pharmaceutical products. Until now, success has been limited to several small molecules and peptides, although remarkable improvements have been accomplished in some of these cases. For example, twice-a-year depot injections with leuprolide are available compared to the once-a-day injection of the solution dosage form. Injectable depots are typically prepared by encapsulation of the drug in poly(lactic-co-glycolic acid) (PLGA), a polymer that is used in children every day as a resorbable suture material, and therefore, highly biocompatible. PLGAs remain today as one of the few “real world” biodegradable synthetic biomaterials used in US FDA-approved parenteral long-acting-release (LAR) products. Despite their success, there remain critical barriers to the more widespread use of PLGA LAR products, particularly for delivery of more peptides and other large molecular drugs, namely proteins. In this review, we describe key concepts in the development of injectable PLGA controlled-release depots for peptides and proteins, and then use this information to identify key issues impeding greater widespread use of PLGA depots for this class of drugs. Finally, we examine important approaches, particularly those developed in our research laboratory, toward overcoming these barriers to advance commercial LAR development.

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“…This is due to the loss of 3D structure and aggregation of immunogens during the synthesis of polymeric particles, which typically introduces organic solvents and high mechanical and/or chemical stresses to cargo materials [51]. New approaches to formulation of biologics into PLGA particles include a 'self-healing encapsulation' procedure that exploits the polymer's transition temperature to load antigens into preformed PLGA particles in an aqueous condition, thus avoiding the loss of their antigenicity and immunogenicity [52,53] On the other hand, recent studies have reported successful surface modification of recombinant Env trimers on synthetic lipid vesicles in an orientationspecific manner [54,55]. Using Ni-NTA-functionalized lipids, Env gp140 trimers with terminal polyhistidine tags (Histag) were anchored to the surfaces of interbilayer-crosslinked multilamellar vesicles (ICMVs).…”

Section: Synthetic Nanoparticles For Presentation Of Hiv-1 Antigensmentioning

confidence: 99%

Vaccine Nanoparticles for Protection Against HIV Infection

Aikins

Bazzill

Moon

2017

Nanomedicine (Lond.)

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The development of a successful vaccine against HIV is a major global challenge. Antiretroviral therapy is the standard treatment against HIV-1 infection. However, only 46% of the eligible people received the therapy in 2015. Furthermore, suboptimal adherence poses additional obstacles. Therefore, there is an urgent need for an HIV-1 vaccine. The most promising clinical trial to date is Phase III RV144, which for the first time demonstrated the feasibility of vaccine-mediated immune protection against HIV-1. Nevertheless, its 31% efficacy and limited durability underscore major hurdles. Here, we discuss recent progress in HIV-1 vaccine development with a special emphasis on nanovaccines, which are at the forefront of efforts to develop a successful HIV-1 vaccine.

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Self‐Healing Microencapsulation of Biomacromolecules without Organic Solvents

Cited by 79 publications

References 22 publications

Biomaterials for Nanoparticle Vaccine Delivery Systems

Biomaterials for Nanoparticle Vaccine Delivery Systems

Injectable controlled release depots for large molecules

Vaccine Nanoparticles for Protection Against HIV Infection

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