Ocular delivery systems for poorly soluble drugs: an in-vivo evaluation.
For highly potent but poorly water-soluble drugs like cyclosporine A, the development of aqueous formulations providing an increase of corneal drug tissue levels, and thus of bioavailability, to increase patient compliance is still a challenge. Therefore, we designed two water-based liquid application systems, an in-situ nanosuspension (INS) and a micellar solution (MS), and tested both formulations in vivo at the rabbit cornea for tolerability and the tissue uptake of CsA. The evaluation of the biological tolerability by periodical eye examination during 180 min and quantification in a defined grading system revealed that the INS evoked minimal to no irritations whereas the MS was perfectly tolerated. After the observation period, the rabbits were sacrificed and the corneal tissue levels of CsA were analyzed. The INS and the MS both showed high levels of 1683±430 ngCsA/gcornea and 826±163 ngCsA/gcornea, respectively, and exceeded drug tissue levels reported for Restasis(®) (350 ngCsA/gcornea) and cationic emulsions (750 ngCsA/gcornea). These results marked our INS and MS as outstanding novel approaches for the treatment of inflammatory corneal diseases.
['Luschmann|C|C|', 'Herrmann|W|W|', 'Strauss|O|O|', 'Luschmann|K|K|', 'Goepferich|A|A|']
D060433:Administration, Ophthalmic D000818:Animals D003315:Cornea D016572:Cyclosporine D016503:Drug Delivery Systems D008297:Male D008823:Micelles D053758:Nanoparticles D009883:Ophthalmic Solutions D011817:Rabbits D012995:Solubility D013535:Suspensions
Cyclosporine A Bioavailability In-situ nanosuspension Biocompatibility Dry eye disease Surfactant micelles