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Non-parenteral drug delivery systems using biomaterials have advantages over traditional parenteral strategies. For ocular and intranasal delivery, nanoparticulate systems must bind to and permeate through mucosal epithelium and other biological barriers. The incorporation of mucoadhesive and permeation-enhancing biomaterials such as chitosan facilitate this, but tend to increase the size and polydispersity of the nanoparticles, making practical optimization and implementation of mucoadhesive nanoparticle formulations a challenge. In this study, we adjusted key poly(lactic-co-glycolic) acid (PLGA) nanoparticle formulation parameters including the organic solvent and co-solvent, the concentration of polymer in the organic phase, the composition of the aqueous phase, the sonication amplitude, and the inclusion of chitosan in the aqueous phase. By doing so, we prepared four statistically unique size groups of PLGA NPs and equally-sized chitosan-PLGA NP counterparts. We loaded simvastatin, a candidate for novel ocular and intranasal delivery systems, into the nanoparticles to investigate the effects of size and surface modification on drug loading and release, and we quantified size- and surface-dependent changes in mucoadhesion in vitro. These methods and findings will contribute to the advancement of mucoadhesive nanoformulations for ocular and nose-to-brain drug delivery.

Chitosan/poly(lactic-co-glycolic)acid Nanoparticle Formulations with Finely-Tuned Size Distributions for Enhanced Mucoadhesion