ASSESSMENT OF A MODEL FOR MEASURING DRUG DIFFUSION THROUGH IMPLANT-GENERATED FIBROUS CAPSULE MEMBRANES

Fibrous tissue, which encapsulates subcutaneously implanted silastic, vinyl, polyurethane and Teflon(R) discs in rats, has been isolated, characterized and tested for drug permeability in order to develop an in vitro model for determining the effect of this tissue on drug disposition from implant sites. With all materials, capsule tissue thickness and collagen content (approximately 59%) was consistent from 2 to 4 months after implantation. Silastic implants afforded the most consistent and usable tissue in terms of thickness and lack of vascularity, and these capsule membranes were used for determining the transport of three model compounds in an in vitro diffusion cell model. The rank ordering of permeability through these membranes was estrone (60.2 x 10(-6) cm s(-1)) > 3-O-methylglucose (18.7 x 10(-6) cm s(-1)) > dextran of molecular weight 70 000 (5.6 x 10(-6) cm s(-1)), which is consistent with expectations based on the molecular weights and partitioning behaviour of the model compounds. The results of these studies indicate that implant-generated encapsulating membranes can be successfully isolated and employed to study drug diffusion in an in vitro model, providing a direct assessment of the barrier properties of encapsulating membranes.