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The development of safe and effective vaccines for cancer and infectious diseases remains a major goal in public health. Over the last two decades, controlled release of vaccine antigens and immunostimulant molecules has been achieved using nanometer or micron-sized delivery vehicles synthesized using biodegradable polymers. In addition to achieving a depot effect, enhanced vaccine efficacy using such delivery vehicles has been attributed to efficient targeting of antigen presenting cells such as dendritic cells. Biodegradable and biocompatible poly(lactic acid) and poly(lactic-co-glycolic acid) polymers belong to one such family of polymers that have been a popular choice of material used in the design of these delivery vehicles. This review summarizes research findings from ourselves and others highlighting the promise of poly(lactic acid)- and poly(lactic-co-glycolic acid)-based vaccine carriers in enhancing immune responses.

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Poly(lactic acid) (PLA) nanoparticles (NPs) are widely investigated due to their bioresorbable, biocompatible and low immunogen properties. Interestingly, many recent studies show that they can be efficiently used as drug delivery systems or as adjuvants to enhance vaccine efficacy. Our work focuses on the molecular mechanisms involved during the nanoprecipitation of PLA NPs from concentrated solutions of lactic acid polymeric chains, and their specific interactions with biologically relevant molecules. In this study, we evaluated the ability of a PLA-based nanoparticle drug carrier to vectorize either vitamin E or the Toll-like receptor (TLR) agonists Pam1CSK4 and Pam3CSK4, which are potent activators of the proinflammatory transcription factor NF-κB. We used dissipative particle dynamics (DPD) to simulate large systems mimicking the nanoprecipitation process for a complete NP. Our results evidenced that after the NP formation, Pam1CSK4 and Pam3CSK4 molecules end up located on the surface of the particle, interacting with the PLA chains via their fatty acid chains, whereas vitamin E molecules are buried deeper in the core of the particle. Our results allow for a better understanding of the molecular mechanisms responsible for the formation of the PLA NPs and their interactions with biological molecules located either on their surfaces or encapsulated within them. This work should allow for a rapid development of better biodegradable and safe vectorization systems with new drugs in the near future.

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