Abstract
Purpose :
Topical drops are widely used for treating ocular diseases despite only 5% of drug reaching the anterior structures of the eye. Due to dynamic barriers, including rapid tear turnover, topical treatments require frequent dosing leading to poor compliance and delayed efficacy. Block copolymer micelles with mucoadhesive phenylboronic acid (PBA) in the outer shell have increased retention time and drug bioavailabilty in ocular tissues, offering a solution to this problem. Here we demonstrate the efficacy of mucoadhesive micelles in an animal model of dry eye disease (DED).
Methods :
Copolymers synthesized by RAFT, and more recently via free radical polymerization, contain various PBA mole percentages. Composition and molecular weight were determine using pNMR. Micelles were formed by precipitation into purified water from acetone. Dry eye was induced in female, Brown Norway rats through the secretion of 25 mg scopolamine/day from subcutaneous micro-osmotic pumps in desiccating conditions. The mucoadhesive micelles were compared to the current DED industry leader, Restasis, through tear volume measured with phenol red threads and corneal fluorescein staining scored using a modified Oxford schema.
Results :
The dry eye model shows 0.075% and 0.1% Cyc-A loaded micelles applied twice a day resolved dry eye symptoms comparable to Restasis, dosed as prescribed. When dosing was extended to once every three days, Restasis was no longer efficacious while the micelles were able to resolve dry eye by all metrics tested, demonstrating the prolonged action of the micelle formulation. Micelles were also administered once every five days, with resolution of tear volume. While there is a statistically significant (p<0.5) difference between fluorescein staining of controls and micelles dosed every 5 days, baseline levels were not obtained.
Conclusions :
Mucoadhesive micelles offer significant potential to increase the efficacy of topically applied ophthalmic drugs by decreasing the dosage, frequency of dose, and off-target systemic toxicity. We have demonstrated in a diseased animal model that these micelles prolong the effect of active therapeutic agents, allowing us to decrease dosing.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.