EFFECT OF CYCLOSPORINE-A FORMULATIONS ON BOVINE CORNEAL ABSORPTION - EX-VIVO STUDY

The purpose of this study was to evaluate, in an er-vivo study, the ab sorption of cyclosporine A on bovine cornea after 24 h contact with va rious drug delivery systems containing 1% cyclosporine A and in compar ison with an olive oil formulation as the reference vehicle for cyclos porine A. The different formulations studied were poly(acrylic acid) p olymeric gels in aqueous/non-aqueous solvents, polyisobutylcyanoacryla te nanocapsules, and a combination of both formulations. The histologi cal effects of these formulations on corneal cells after 24 h of conta ct were also studied. Tile lowest absorption rate of cyclosporine A wa s found using olive oil with a percent absorption of 2.52 +/- 1.52% (2 59 +/- 171 mu g/g cornea). The three formulations developed for this s tudy, nanocapsules, poly(acrylic acid) polymeric gel and nanocapsules gel showed significantly better absorption of CsA than olive oil, with a mean percent absorption of 5.81 +/- 2.04% (621 +/- 218 mu g/g corne al, 603 +/- 2.93% (651 +/- +/- 313 mu g corneal and 7.92 +/- 2.55% (84 7 +/- 273 mu g/g corneal respectively. As we studied the penetration o f cyclosporine A into the different layers of the cornea, we observed that for all formulations, CsA remained at the corneal surface and did not penetrate the whole cornea. The histological study showed that ol ive oil, nanocapsules and poly(:acrylic acid) gel in aqueous/non-aqueo us solvents show some modifications on the cornea, contrary to the nan ocapsules gel which did not indicate any toxic effect. The nanocapsule gel, with the highest percent absorption along with its margin of saf ety on the cornea, seems to present a new promising drug delivery syst em for ocular administration.