Polymeric Micelles for Ocular Drug Delivery

Abstract

Ocular drug delivery to treat diseases of the anterior segment of the eye continues to be a very challenging task. Static barriers include tight junctions of the conjunctiva and dynamic barriers such as the high turnover rate of the tear film contribute to the impenetrable anterior surface. As a result, conventional ophthalmic medication in the form of eye drops is quickly removed and only <5% of the administered dose is efficiently delivered to the anterior tissues. To improve drug delivery into the ocular tissues, we report on a polymeric micelle drug delivery system that may be used to prolong the precorneal residence time of encapsulated drugs. The polymeric micelles were formed from self-assembly of block copolymers composed of poly(L-lactide)-b-polyethylene glycol methacrylate (pLA-b-pEGMA). Atom transfer radical polymerization was used to synthesize these bottlebrush copolymers to increase hydrophilicity, neutrality, surface density and hydrophobic shielding. The micelles were able to achieve an 80% encapsulation efficiency of Cyclosporine A and sustained a release for up to 30 days. By varying the chain lengths of the pLA and pEGMA blocks, micelle sizes ranging from 60-120 nm with a near neutral surface were explored for mucopenetrating properties. These findings illustrate that micelles can reduce the administration frequency, dosage, and side effects associated with conventional eye drops.