Eye-targeted Sustained Delivery of Anti-inflammatory Drugs to Injured Eyes

Abstract

Purpose : Continuous and efficient delivery of anti-inflammatory therapeutics into inflamed ocular tissues can be challenging due to patient compliance as well as structural barriers of the eye. This study is aimed to develop a mucin-targeting eye drop capable of drug delivery in a sustained manner to improve the drugs’ therapeutic efficacy and reduce dose frequency.

Methods : Eye drops were formed by incorporating drug-loaded micelles (MCs) into a hyaluronic acid-based matrix solution. Drug-loaded MCs were formed from the self-assembly of block copolymers with an anti-inflammatory corticosteroid drug, loteprednol etabonate. The phenylboronic acid (PBA) group bearing the block copolymer polyethylene glycol-b-(N-(2-hydroxypropyl) methacrylamide-co-oligolactate) was synthesized by radical polymerization and characterized by proton nuclear magnetic resonance (¹H-NMR). The MCs were characterized by dynamic light scattering and transmission electron microscopy to determine particle size and polydispersity index, surface charge, and mucoadhesive properties. Drug loading efficacy was quantified by high-performance liquid chromatography (HPLC). Eye drops were assessed for viscoelasticity by rheology and for wettability by measuring wetting areas on mucin-coated glass slides.

Results : PBA conjugation efficacy ranged from 24.5% to 97%. The MCs were spherical with a diameter of 109.0 ± 9.2 nm and had a narrow size distribution with a polydispersity index of 0.094 ± 0.01. By increasing drug/polymer ratios, drug loading increased from 55.7 ± 10.0 to 589.2 ± 75.5 µg/mL with no effect on drug loading efficiency. The eye drops showed desirable shear thinning behavior and had a viscosity of 70 cps at a high shear rate (1000 s^-1), pH of 7.4, and wetting areas of 27 ± 0.7 mm² (20 µL). Increasing hyaluronic acid concentrations from 0.1% to 0.5% (w/v) significantly enhanced the viscosity and decreased wetting areas from 43 ± 0.9 to 27 ± 0.7mm² (p<0.0001) while varying glycerin concentrations from 0.3% to 1% (w/v) had little impact on viscosity and wettability.

Conclusions : Drug-loaded MCs with optimal size, loading capacity, and mucoadhesive properties were successfully prepared and formulated as eye drops with suitable viscosity, pH, and wettability. Our targeting eye drops can potentially be used as a treatment for corneal inflammation with improved bioavailability and patient compliance.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.