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New approach in ocular drug delivery: in vitro and ex vivo investigation of cyclodextrin-containing, mucoadhesive eye drop formulations

Background: Optimal transcorneal penetration is necessary for ocular therapy ; meanwhile, it is limited by the complex structure and defensive mechanisms of the eye. Antimicrobial stability of topical ophthalmic formulations is especially important. According to previous studies, the mostly used preservative, benzalkonium-chloride is irritative and toxic on corneal epithelial cells ; therefore, novel non-toxic, antimicrobial agents are required. In this study, prednisolone- containing ophthalmic formulations were developed with expected optimal permeation without toxic or irritative effects. Methods: The toxicity and permeability of prednisolone-containing eye drops were studied on a human corneal epithelial cell line (HCE-T) and ex vivo cornea model. The lipophilic drug is dissolved by the formation of cyclodextrin inclusion complex. Zinc-containing mucoadhesive biopolymer was applied as an alternative preservative agent, whose toxicity was compared with benzalkonium-chloride. Results: As the results show, benzalkonium- chloride- containing samples were toxic on HCE-T cells. The biopolymer caused no cell damage after the treatment. This was confirmed by immunohistochemistry assay. The in vitro permeability was significantly higher in formulations with prednisolone-cyclodextrin complex compared with suspension formulation. According to the ex vivo permeability study, the biopolymer-containing samples had significantly lower permeability. Conclusion: Considering the mucoadhesive attribute of target formulations, prolonged absorption is expected after application with less frequent administration. It can be stated that the compositions are innovative approaches as novel non-toxic ophthalmic formulations with optimal drug permeability.

cyclodextrin ; ex vivo cornea model ; human corneal epithelial cell line ; mucoadhesion ; ocular drug delivery ; prednisolone

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