(341e) Facile and Robust Fabrication of Sub-100nm Poly(lactic-co-glycolic acid) Nanoparticle-Based Drug Delivery Vehicles Via Self-Assembly

Controlled drug release using polymer (most commonly poly(lactic-co-glycolic acid), or PLGA) nanoparticles has achieved great success including clinical validations. However, it has been challenging to produce PLGA-based nanoparticles smaller than 200 nm. It has been well established that smaller particle size leads to superior performance in biodistribution and tumor penetration. Although the “nanoprecipitation method” has been shown to result in smaller particles, in practice this process is difficult to control. Here we report a novel approach, which is based on a bottom-up rather than top-down process, to produce PLGA nanoparticles that have particle sizes well below 100 nm.

            This novel method involves using micelles as a template for self-assembly of PLGA. Amphiphilic poly(styrene-co-ethylene glycol) molecules were mixed with PLGA to form micelles with particle size approximately 50 nm. Because this method is based on self-assembly, the process is highly robust and no external energy input is required. Dexamethasone was used as a model drug to examine the potential of PLGA-micelles for controlled drug release. It was found that, compared with PLGA nanoparticles fabricated by the conventional solvent extraction method, PLGA-micelles led to significantly lower initial drug release burst. Noting that PLGA acts as an encapsulant within the fixed micelle nano-container, this technology offers a simple way to modulate drug release without changing particle size and surface chemistry, which determine the transport behavior of nanoparticles in biological environments.