COLLAGEN AS A DELIVERY SYSTEM FOR HYDROPHOBIC DRUGS - STUDIES WITH CYCLOSPORINE

The time-honored approach to delivering drugs to the ocular surface is through the use of liquid drops and semisolid ointments. Such deliver y systems, however, are not efficient at delivering therapeutic concen trations of drugs to the cornea and intraocularly. Over the past sever al years, we tested the biopolymer, collagen, as a means of delivering both hydrophilic and hydrophobic drugs to the ocular surface. This st udy summarizes results obtained using the hydrophobic drug, cyclospori ne, incorporated into collagen shields and collagen particles. Corn oi l drops containing cyclosporine were used as the control. Groups of an esthetized rabbits were fitted with collagen shields containing cyclos porine, treated topically with collagen particles containing cyclospor ine suspended in an ocular surface lubricant, or given topical drops o f corn oil containing cyclosporine. At intervals after a single treatm ent with one of the drug formulations, corneas, aqueous humor, and blo od were collected for analysis of cyclosporine concentration. With eit her of the two collagen vehicles, peak concentrations of the drug were found in the cornea 4 hours after application. The corn oil vehicle y ielded a significantly lower and earlier peak concentration (1 hour af ter application). By 8 hours, significant amounts of the drug were sti ll present in the corneas of the collagen-treated animals, whereas dru g levels in the corn oil treatment group had returned to baseline. Dru g delivery profiles in the aqueous humor were similar, except that the amounts of drug were five times lower. No cyclosporine was detected i n the blood from any of the treated animals. In other experiments, the ability of cyclosporine in collagen to prevent corneal allograft reje ction 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 t ime course of initiation of the graft reaction was determined by clini cal examination and the number of grafts surviving in each group was r ecorded. Cyclosporine incorporated into collagen particles and collage n shields was more effective in preventing the onset of primary cornea l allograft reaction and the loss of grafts by rejection, compared wit h cyclosporine in corn oil. These results indicate that this biopolyme r is an effective system for the delivery of a hydrophobic drug in the rapeutic concentrations to the cornea.