Prevention of Sugar Cataract Formation by Topical Administration of an Aldose Reductase Inhibitor Formulation

Abstract

Abstract: : Purpose: Cataract formation rapidly develops in young galactose–fed rats and reports to date indicate that topical administration of aldose reductase inhibitors cannot arrest sugar cataracts as adequately as oral administration. This is because topical administrations to date have failed to deliver adequate amounts of inhibitor to the lens. In the topical delivery of drugs, drug retention on the eye surface is of great importance because increased retention on the ocular surface often leads to increased ocular absorption of a drug. The purpose of this study was to maximize the topical delivery of the aldose reductase inhibitor 2–methyl–6–fluorospirochroman–4–5’–imidazolidine–2’, 4’–dione, by developing formulations containing a 3% of this aldose reductase inhibitor (ARI) with five different vehicles comprised of polymers, gums, or viscosity enhancers. Methods: Each formulation of ARI was topically administered twice daily to young, 50 g Sprague Dawley rats fed a 50% galactose diet for 21 days to determine if the amounts of topically delivered ARI were adequate to inhibit sugar cataract formation. Results: In the untreated galactose–fed rats sugar cataract formation rapidly progressed from vacuole formation (∼ 5 days) to cortical opacification (∼ 8 days) and finally hypermature cataracts in which the cortical fibers had liquified with only the nucleus remaining (15 days). Inhibition of sugar cataract formation was observed in all five formulations with the only lenticular changes observed being an enhancement of the posterior sutures suggesting minor lens swelling. The levels of ARI delivered into the lens by these 5 formulations was also determined. Each ARI formulation was topically administered twice daily for a period of seven days to similar young rats fed a normal, control diet and the levels of drug were determined by HPLC analysis in the excised lenses. Conclusions:The highest lenticular levels of the ARI, determined by HPLC, were obtained with 0.25% Carbopol + 0.25 % hydroxypropyl methylcellulose (HPMC) as vehicles followed by 0.5% gellan gum, 0.5% HPMC, 0.25% Carbopol, and 0.5% xanthan gum.

Keywords: cataract • drug toxicity/drug effects