Tuning the Size of Poly(lactic-co-glycolic Acid) (PLGA) Nanoparticles Fabricated by Nanoprecipitation

摘要

Polymeric nanoparticles (PNPs) are promising drug carriers in cancer treatment. Size of the particles has a significant impact on drug loading, in vivo distribution, extravasation, intratumor diffusion and cell uptake, and thus is critical for the successful development of a drug delivery regime. However, methods for manufacturing PNPs of defined size are yet to be established. The goal of this study is to establish a method that can be used to fabricate PNPs with controlled size. The factors that could impact the size of PNPs fabricated by nano-precipitation are systematically investigated. The factors studied include polymer concentration, organic solvent, temperature, aqueous phase ionic strength, organic phase injection rate, aqueous phase agitation rate, gauge of the needles, and final polymer concentration. Polymer concentration, the choice of organic solvent, temperature, and the ionic strength of the aqueous phase are shown to have a significant impact on the size of PNPs, and the effect of these factors can be attributed to a single parameter, the diffusion coefficient of the solvent in water, D-pw. It is possible that by tightly control these four parameters, nanoparticles with highly predictable and desirable size with narrow size distribution can be fabricated.