Mucoadhesive Micellar Eyedrop for Sustained Delivery of Anti-inflammatory Drugs to Injured Eyes

Abstract

Purpose : Ocular inflammation is one of the leading causes of blindness worldwide, and corticosteroid eye drops (e.g., loteprednol etabonate (LE) drops) are the mainstay of therapy. However, achieving sustained delivery of anti-inflammatory drugs into ocular tissues is challenging due to anatomical and physiological barriers. High frequency of eyedrop administration also results in poor patient adherence. This study aims to develop a mucin-targeting eye drop capable of sustained drug delivery with improved therapeutic efficacy.

Methods : Drug-loaded micelles (LE-MCs) were formed from self-assembly of phenylboronic acid groups bearing block copolymers with LE. Physicochemical properties were characterized by dynamic light scattering and liquid chromatography. Mucoadhesive eye drops were formed by incorporating LE-MCs into a hyaluronic acid-based matrix and the biocompatibility was assessed using human corneal epithelial cells. In vivo efficacy of LE-MCs (1X/day) was evaluated using a mouse model of electrocautery inflammation and compared to commercial LE drops (4X/day) and no treatment. Corneal opacity scores were accessed by analysis of Slit Lamp photos and central corneal thickness (CCT) was measured via Optical Coherence Tomography.

Results : LE-MCs had a narrow size distribution with a diameter of 133.8±0.8 nm and a polydispersity index of 0.04. The drug encapsulation efficacy and loading capacity of LE-MCs were 45.8±2.0% and 4.6±0.2%, respectively. The in vitro drug release profile of LE-MCs showed an initial burst release (51.9±3.9% on Day 1) followed by a slow release phase for 12 days. Cells treated with the matrix containing MCs exhibited high viability (>95%) and continued proliferation over 5 days. The percentage of mice with an opacity score ≥3 on day 7 for LE drops, LE-MCs, and no treatment group were 11%, 0%, and 50%, respectively. Mice (%) with ≥20% CCT increase over 7 days for LE drops, LE-MCs, and no treatment group were 10%, 10%, and 100%, respectively. On day 7, both LE drops (103.7±11.5%, p=0.039) and LE-MCs (107.3±13.4%, p=0.009) treatment resulted in significantly lower CCT change compared to no treatment (213.0±152.9%).

Conclusions : LE-MCs showed suitable size, optimal drug release, and excellent biocompatibility. Our mucoadhesive eye drops may eliminate the need for intensive administration of eye drops and hold promise as a safe and efficient solution for corneal inflammation.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.