Core-Shell Arginine-Containing Chitosan Microparticles for Enhanced Transcorneal Permeation of Drugs

Chitosan oligosaccharide (C) was functionalized with L-arginine (A) and short hydrocarbon chains (C-8) to design an amphiphilic copolymer, henceforth CAC(8), leading to microparticles (MPs) consisting of an arginine-decorated hydrophilic shell and inner hydrophobic domains allowing the encapsulation of high amount hydrophobic drugs such as sorafenib tosylate (>10% w/w). L-arginine side chains were selected in order to impart the final MPs enhanced transcorneal penetration properties, thus overcoming the typical biological barriers which hamper the absorption of drugs upon topical ocular administration. The mucoadhesive properties and drug release profile of the CAC(8) MPs (CAC(8)-MPs) were studied, showing that CAC(8)-MPs can strongly interact with mucin, and thus gradually release their payload in situ to potentially improve the bioavailability of the drug after topical administration. In vitro transcorneal studies also showed that CAC(8)-MPs are endowed with effective permeation enhancer ability combined with negligible toxicity. (c) 2019 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.