Controlled polymerization for drug delivery to the eye

Abstract

ABSTRACT

Effective drug delivery to ocular tissues is an unmet challenge that has significant potential to improve the treatment of ocular diseases. Whether the intended drug delivery target is the anterior or posterior segment, the eye’s efficient natural protection mechanisms prevent effective and sustained drug delivery. Anatomical and physiological barriers including the rapid tear turnover that effectively washes away topically applied drugs, the impermeable characteristics of the cornea, conjunctiva, and sclera, and the tight junctions in the blood-ocular barriers make conventional drug delivery methods ineffective. New materials that are able to overcome these barriers are essential to improving the sustained delivery of ophthalmic therapeutics to the intended targets within the eye. This thesis will explore two polymeric drug delivery systems that have the potential to improve therapeutic delivery to ocular tissues. Chapter 1 will discuss the anatomical and physiological barriers to ophthalmic drug delivery and overview current research in this area. Chapter 2 will discuss the synthesis of N-isopropylacrylamide-based copolymers with adjustable gelation temperatures based on composition and molecular weight. Chapter 3 will discuss further development of these copolymers into an injectable, thermoresponsive, and resorbable polymeric drug delivery system intended for the treatment of diseases in the posterior segment. Chapter 4 will discuss the development of mucoadhesive polymeric micelle nanoparticles based on phenylboronic acid intended for topical administration of ophthalmic therapeutics. Finally, Chapter 5 will provide an overview of potential future work on these materials that could further develop and broaden their therapeutic use.