A novel cyclosporin A micelle formulation for topical ophthalmic applications: development, biocompatibility, corneal penetration, and efficacy studies

The preparation of a cyclosporin A (CsA) aqueous formulation for topical ophthalmic delivery is a challenge for two main reasons: the physicochemical characteristics of this potent immuno-suppressant make it difficult to solubilize the drug in aqueous media, and the eyes' protective mechanisms and barriers enormously decrease the drug bioavailability in tissues when topically applied. This thesis addresses both pharmaceutical challenges by developing a novel aqueous formulation based on polymeric micelles of poly(ethylene glycol)-hexylsubstituted poly(lactide) block copolymers, which efficiently incorporate CsA and facilitate their aqueous dissolution. The novel formulation showed excellent ocular tolerance and biocompatibility. Furthermore, the micellar drug carriers were able to accumulate in all corneal layers, forming a drug reservoir for a targeted release of CsA. The efficacy was demonstrated in vivo in rats in the prevention of corneal allograft rejection, for which the obtained success rate was the same as it was achieved with a CsA systemic administration