Liposome-encapsulated mitomycin C for the reduction of corneal healing rate and ocular toxicity

Mitomycin-C (MMC), a potent antibiotic-antineoplastic drug, has recently proven to be useful as additional treatment in ocular surgery (pterygium, glaucoma filtering, photorefractive laser keratectomy, etc.) when inhibiting the epithelial wound healing response and reducing surgical scarring is beneficial to surgical success. However, the therapeutic benefits of MMC are frequently offset by ocular toxicity and undesirable side effects (retinal toxicity, corneal edema, corneal perforation, cataract, secondary glaucoma, iritis, scleral calcification, pain, etc.). The purpose of this study was to evaluate if a liposomal preparation containing MMC was capable of reducing the corneal healing rate and drug toxicity of a corneal lesion in a rabbit model. To do this, a liposomal formulation containing 0.2 mg/ml of MMC was prepared and tested against aqueous solutions and viscous formulations based on tamarind seeds polysaccharide (TSP), which were used as references. In vitro release of MMC from the vehicles through a dialysis membrane was characterized by a fast diffusion of MMC from the aqueous solution, while a more gradual release from the TSP and the liposomal formulations was observed. To evaluate the intraocular penetration of MMC, the drug amount in the aqueous and vitreous humor of the animals was determined 60 min after treatment. MMC toxicity was analyzed by monitoring the proliferation and viability of a rabbit corneal epithelial cell line (RCE) in the different formulations under study. These results showed reduced cytotoxicity for MMC in TSP viscous vehicles; however, only the liposomal MMC vehicle appeared to produce both lower toxicity for a rabbit corneal epithelial cell line (RCE) culture and a substantial reduction of the corneal healing rate in vivo.