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Microfluidic System for the High-Throughput Reproducible Synthesis of Therapeutic Polymeric Nanoparticles

P.M. Valencia, M. Rhee, R. Langer, O. Farokhzad, R. Karnik
Massachusetts Institute of Technology, US

Keywords: nanoparticles, high-throughput, screening, microfluidics


Polymeric nanoparticles (NPs) comprised of poly(lactide-co-glycolide)-b-polyethyleneglycol (PLGA-PEG) block copolymers are promising drug delivery vehicles with the advantages of controlled drug release, enhanced stability, and ability to carry thousands of drug molecules per NP. Such NPs can be targeted to differentially deliver drugs to the site of interest in the body, translating to improvement in the therapeutic index of drugs. However, physicochemical properties of NPs such as size, charge, surface chemistry, payload, and targeting ligand density significantly affect the biodistribution of the drug, and the delicate balance between each these properties needs to be experimentally determined and precisely engineered for ultimate in vivo success [3]. Here we report the development of a microfluidic system that enables reproducible, high-throughput preparation of a library of distinct homogeneous, PLGA-PEG NPs. We demonstrate the ability to synthesize and in vitro screen tens of different NP formulations per day by integrating our microfluidic technology with high-throughput flow cytometry (FACS). This makes an optimal system for the translation of nanovehicles to in vivo applications. To the best of our knowledge, this is the first time a microfluidic system is developed for the synthesis and screening of polymeric nanovehicles for drug development applications.
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