Optimization of Mucoadhesive Polymer Micelles for Drug Delivery and Ophthalmic Formulations

Abstract

Nanotechnology enable medicine (nanomedicine) is expected to be the next advent of the health care market, facilitating efficient, safe, and personalized therapies. But there has been limited success penetrating the market. Despite numerous publications demonstrating the utility of nanoparticle platforms for drug delivery, analyses on commercial viability show there are several challenges to be addressed. This thesis work addresses some of these challenges, with a focus on ocular drug delivery. Topical administration is the most popular route of ocular drug delivery. However, only 5% of the administered dose is bioavailable for action at the target site, while the remaining 95% is removed via blinking, nasolacrimal drainage, or degradation. Frequent administrations of concentrated solutions are required to overcome these barriers to maintain therapeutic concentrations. Self-assembled mucoadhesive polymer nanoparticles (MNPs) composed of a poly(lactic acid) core, and dextran corona functionalized with phenylboronic acid have been successful in addressing some of these challenges for ocular drug delivery. This work is intended to optimize the commercial viability of these nanoparticle drug carriers. A review of the current state of nanomedicine for ocular drug delivery aimed at improving retention on the ocular surface is presented. The manufacturing process of the mucoadhesive block copolymer is investigated and optimized resulting in significant time and cost savings. In addition, a method for modification of carbohydrates without the use of organic solvents based on solid-state chemistry is described. Strategies to improve the shelf-life of the colloid suspension are explored and optimized for the MNPs with pharmacopoeia guidelines. A novel method of utilizing freeze-drying to drive self-assembly of polymer micelles is demonstrated. Further steps to improve the commercial viability and success of the MNP platform are discussed in the conclusions.