Mucoadhesive micelles for ophthalmic drug delivery.

Abstract

The most common formulation for treating ocular conditions is topical eyedrops, despite their well-documented inefficiency. In this study, mucoadhesive nano-micelles were developed to overcome the poor efficacy of topical eyedrops in the treatment of dry eye disease. The micelles contained a pre-activated thiomer capable of releasing mucolytic N-acetylcysteine upon covalent disulfide exchange with the natural mucus layer which covers the surface of the eye. The micelles, approximately 70 nm in diameter, were shown to be mucoadhesive through zeta potential analysis. The critical micelle concentration was determined to be 217 mg/L using the pyrene fluorescence method. The core of the micelles was loaded with cyclosporine A, displaying a greater than 90% entrapment efficiency, and yielding sustained release of approximately 57% over 10 days. The cellular response to the micelles was tested with human corneal epithelial cells by MTT assay and Live/Dead staining. It was found that lower concentrations of the amphiphilic polymer resulted in greater cellular viability and in all cases, viability increased from 24 to 48 h following treatment. Overall, these mucoadhesive systems have potential to provide more efficacious treatment of anterior segment ocular conditions.