Christoph Luschmann1, Joerg Tessmar, Simon Schoeberl, Olaf Strauß, Karl Luschmann, Achim Goepferich. 1. *Department of Pharmaceutical Technology, University of Regensburg, Regensburg, Germany; †Department for Functional Materials in Medicine and Dentistry, University of Wuerzburg, Wuerzburg, Germany; ‡Department of Experimental Ophthalmology, University Hospital Regensburg, Regensburg, Germany; §Experimental Ophthalmology, Department Ophthalmology, Charité University Medicine Berlin, Berlin, Germany; and ¶Pharma Stulln GmbH, Stulln, Germany.
Abstract
PURPOSE: In this study, we developed a self-assembling micellar system to deliver cyclosporine A (CsA) in an aqueous solution to the cornea. METHODS: Two nonionic surfactants of the poly(ethylene glycol)-fatty alcohol ether type (Sympatens AS and Sympatens ACS) were characterized in terms of micelle size, shape, and charge, and their encapsulation efficiency for CsA. In an in situ single dose bioavailability study, the corneal CsA levels were determined in an enucleated porcine eye model. A commercial formulation and a 2% CsA olive oil solution served as references. RESULTS: Both surfactants formed spherical micelles with a size of 9 to 12 nm in water. A concentration as low as 0.3% (wt/vol) Sympatens AS was sufficient to entrap therapeutic levels of at least 0.1% (wt/vol) CsA. In the porcine in situ model, exceptionally high drug levels in the cornea were obtained for the micellar CsA solution (1557 ± 407 ngCsA/gcornea). They were significantly higher than those of Restasis (545 ± 137 ngCsA/gcornea) or the olive oil solution (452 ± 142 ngCsA/gcornea). CONCLUSIONS: In conclusion, we have shown a promising simple and efficient approach for the application of CsA in an aqueous solution to the cornea to treat inflammatory corneal diseases.
PURPOSE: In this study, we developed a self-assembling micellar system to deliver cyclosporine A (CsA) in an aqueous solution to the cornea. METHODS: Two nonionic surfactants of the poly(ethylene glycol)-fatty alcohol ether type (Sympatens AS and Sympatens ACS) were characterized in terms of micelle size, shape, and charge, and their encapsulation efficiency for CsA. In an in situ single dose bioavailability study, the corneal CsA levels were determined in an enucleated porcine eye model. A commercial formulation and a 2% CsAolive oil solution served as references. RESULTS: Both surfactants formed spherical micelles with a size of 9 to 12 nm in water. A concentration as low as 0.3% (wt/vol) Sympatens AS was sufficient to entrap therapeutic levels of at least 0.1% (wt/vol) CsA. In the porcine in situ model, exceptionally high drug levels in the cornea were obtained for the micellar CsA solution (1557 ± 407 ngCsA/gcornea). They were significantly higher than those of Restasis (545 ± 137 ngCsA/gcornea) or the olive oil solution (452 ± 142 ngCsA/gcornea). CONCLUSIONS: In conclusion, we have shown a promising simple and efficient approach for the application of CsA in an aqueous solution to the cornea to treat inflammatory corneal diseases.