Collagen as a Delivery System for Hydrophobic Drugs: Studies with Cyclosporine

Abstract

ABSTRACT

The time-honored approach to delivering drugs to the ocular surface is through the use of liquid drops and semisolid ointments. Such delivery systems, however, are not efficient at delivering therapeutic concentrations of drugs to the cornea and intraocularly. Over the past several years, we tested the biopolymer, collagen, as a means of delivering both hydrophilic and hydrophobic drugs to the ocular surface. This study summarizes results obtained using the hydrophobic drug, cyclosporine, incorporated into collagen shields and collagen particles. Corn oil drops containing cyclosporine were used as the control. Groups of anesthetized rabbits were fitted with collagen shields containing cyclosporine, treated topically with collagen particles containing cyclosporine suspended in an ocular surface lubricant, or given topical drops of corn oil containing cyclosporine. At intervals after a single treatment with one of the drag formulations, corneas, aqueous humor, and blood were collected for analysis of cyclosporine concentration. With either of the two collagen vehicles, peak concentrations of the drug were found in the cornea 4 hours after application. The corn oil vehicle yielded a significantly lower and earlier peak concentration (1 hour after application). By 8 hours, significant amounts of the drug were still present in the corneas of the collagen-treated animals, whereas drug levels in the corn oil treatment group had returned to baseline. Drug delivery profiles in the aqueous humor were similar, except that the amounts of drag were five times lower. No cyclosporine was detected in the blood from any of the treated animals. In other experiments, the ability of cyclosporine in collagen to prevent corneal allograft rejection in two high-risk models of corneal transplantation was evaluated. Groups of rabbits were given allogeneic corneal transplants and were then treated prophylactically with cyclosporine in collagen shields, cyclosporine in collagen particles, or cyclosporine in corn oil. The time course of initiation of the graft reaction was determined by clinical examination and the number of grafts surviving in each group was recorded. Cyclosporine incorporated into collagen particles and collagen shields was more effective in preventing the onset of primary corneal allograft reaction and the loss of grafts by rejection, compared with cyclosporine in corn oil. These results indicate that this biopolymer is an effective system for the delivery of a hydrophobic drug in therapeutic concentrations to the cornea.