Phenylboronic-Acid-Based Polymeric Micelles for Mucoadhesive Anterior Segment Ocular Drug Delivery

Topical drug delivery to the front of the eye is extremely inefficient due to effective natural protection mechanisms such as precorneal tear turnover and the relative impermeability of the cornea and sclera tissues. This causes low ocular drug bioavailability, requiring large frequent doses that result in high systemic exposure and side effects. Mucoadhesive drug delivery systems have the potential to improve topical drug delivery by increasing pharmaceutical bioavailability on the anterior eye surface. We report the synthesis and characterization of a series of poly(L-lactide)-b-poly(methacrylic acid-co-3-acrylamidophenylboronic acid) block copolymer micelles for use as mucoadhesive drug delivery vehicles. Micelle properties, drug release rates, and mucoadhesion were shown to depend on phenylboronic acid content. The micelles showed low in vitro cytotoxicity against human corneal epithelial cells and undetectable acute in vivo ocular irritation in Sprague-Dawley rats, suggesting good biocompatibility with the corneal surface. The micelles show the potential to significantly improve the bioavailability of topically applied ophthalmic drugs, which could reduce dosage, frequency of administration, and unintentional systemic exposure. This would greatly improve the delivery of the ocular drugs such as the potent immunosuppressive cyclosporine A used in the treatment of severe dry eye disease.