Effect of cyclosporine A formulations on bovine corneal absorption: ex-vivo study.
The purpose of this study was to evaluate, in an ex-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 formulation on corneal cells after 24 h of contact were also studied. The lowest absorption rate of cyclosporine A was found using olive oil with a percent absorption of 2.52 +/- 1.52% (259 +/- 171 micrograms/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 micrograms/g cornea), 6.09 +/- 2.93% (651 +/- 313 micrograms cornea) and 7.92 +/- 2.55% (847 +/- 273 micrograms/g cornea) 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 nonocapsules 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.
Le Bourlais
C A
CA
Laboratoire de Pharmacie Galénique, Biopharmacie et Pharmacie Clinique, Faculté de Pharmacie, Université de Rennes I, France.
Chevanne
F
F
Turlin
B
B
Acar
L
L
Zia
H
H
Sado
P A
PA
Needham
T E
TE
Leverge
R
R
D000180:Acrylic Resins; D000327:Adsorption; D000818:Animals; D002214:Capsules; D002417:Cattle; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D016503:Drug Delivery Systems; D005782:Gels; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D066298:In Vitro Techniques; D000069463:Olive Oil; D009883:Ophthalmic Solutions; D010938:Plant Oils
D000180:Acrylic Resins; D002214:Capsules; D005782:Gels; D007166:Immunosuppressive Agents; D000069463:Olive Oil; D009883:Ophthalmic Solutions; D010938:Plant Oils; C006903:carbopol 940; D016572:Cyclosporine