New Approach in Ocular Drug Delivery: In vitro and ex vivo Investigation of Cyclodextrin-Containing, Mucoadhesive Eye Drop Formulations

Abstract

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.

Design and Optimization of In Situ Gelling Mucoadhesive Eye Drops Containing Dexamethasone

“…After 30 min of treatment, cell viability was measured. The results showed no sign of cytotoxicity [ 48 ]. ZnHA (0.15%) is also used in a commercially available eye drop.…”

In Vitro and Ex Vivo Models for Assessing Drug Permeation across the Cornea

“…Statens Seruminstitut rabbit corneal cells (SIRC) and HCE-T (human corneal epithelial cell-transformed cell line) cells are the most commonly used immortalized cells in corneal toxicology, transport, and permeability research. ,,− The SIRC cell line was the first immortalized cell line derived from corneal tissue. Although, these cells have been isolated from rabbit corneas in 1957, their origin is unknown, and there are no records of their first 400 passages .…”

“…The limitation of this model is that it does not include the stroma or endothelial cells. As pointed out by Bíro et al, who compared the uptake of cyclodextrins in an in vitro epithelial corneal model and an ex vivo diffusion cell, permeability was substantially higher in the in vitro model, because this model only contained the corneal epithelium . Furthermore, another drawback is that the wing cells and basal cells in the cultured epithelium are not as well organized as they are in the intact cornea, this is significant since appropriate organization of these cells is necessary for maintaining the cornea’s integrity and function…”

Development of Carvedilol Nanoformulation-Loaded Poloxamer-Based In Situ Gel for the Management of Glaucoma

“…Ex vivo corneal permeability across freshly excised rabbit cornea was investigated using the membrane diffusion method [43]. Briefly, the excised cornea was sandwiched between the donor and receptor compartments of Franz diffusion cell.…”