Journal of Microencapsulation, Vol.14, No.4, 457-467, 1997
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 absorption of cyclosporine A on bovine cornea after 24 h contact with various drug delivery systems containing 1% cyclosporine A and in comparison with an olive oil formulation as the reference vehicle for cyclosporine A. The different formulations studied were poly(acrylic acid) polymeric gels in aqueous/non-aqueous solvents, polyisobutylcyanoacrylate nanocapsules, and a combination of both formulations. The histological effects of these formulations on corneal cells after 24 h of contact were also studied. Tile lowest absorption rate of cyclosporine A was found using olive oil with a percent absorption of 2.52 +/- 1.52% (259 +/- 171 mu g/g cornea). The three formulations developed for this study, 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 corneal, 603 +/- 2.93% (651 +/- +/- 313 mu g corneal and 7.92 +/- 2.55% (847 +/- 273 mu g/g corneal respectively. As we studied the penetration of 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 olive oil, nanocapsules and poly(:acrylic acid) gel in aqueous/non-aqueous solvents show some modifications on the cornea, contrary to the nanocapsules gel which did not indicate any toxic effect. The nanocapsule gel, with the highest percent absorption along with its margin of safety on the cornea, seems to present a new promising drug delivery system for ocular administration.
Keywords:TOPICAL CYCLOSPORINE;OCULAR PHARMACOKINETICS;COLLAGENSHIELDS;AQUEOUS-HUMOR;RABBIT EYE;PENETRATION;REJECTION;NANOCAPSULES;EYEDROPS;SURVIVAL