Drug delivery within the brain is extremely challenging because of difficulties surmounting the blood brain barrier and the low diffusion constant of most drugs within brain. Nanoparticle drug carriers may provide a solution; however, fabrication of uniform sub-100 nm particles, the optimal size for circulation and uptake, can be challenging. Here, we report on a composite nanoparticle drug delivery carrier that combines features of two of the most popular nano-drug delivery systems: poly(lactic-co-glycolic acid) (PLGA) nanoparticles and polymer micelles. PLGA nanoparticles are biocompatibile, display tunable degradation times, and tunable mechanical properties. However, synthesis of sub-100 nm PLGA nanoparticles has proven difficult. In contrast, self-assembled micelle-based drug delivery vehicles can easily achieve the required sub‑100 nm size.<br/><br/>Inspired by the uniformity of micelle drug carriers, we used poly(styrene-block-ethylene oxide) (PS-PEO) block co-polymers to template the formation of PLGA nanoparticles, yielding PolyDots that integrate the features of conventional PLGA particles with the tightly-controlled synthesis of micelles by self-assembly. PolyDot release characteristics were evaluated using a model anti-inflammatory drug, dexamethasone, and PolyDots showed decreased burst release compared to traditional PLGA particles and increased drug loading compared to micelles without PLGA. Drug loading and release rate could be tuned by varying the PLGA concentration. For targeted delivery, PolyDots were also modified with a molecule targeting transferrin receptor, which is upregulated in cancer, and cells were shown to internalize these particles. Thus, PolyDots offer a potential targeted delivery carrier with sub‑100 nm, uniform size that incorporates biodegradable and tunable release characteristics.

Synthesis and characterization of a micelle-templated, sub-100 nm PLGA nanoparticle for targeted drug delivery

249th National Meeting (2015)

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