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.

Keywords:

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

Author Contributions

All authors contributed to the data analysis, drafting, or revising of the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no conflicts of interest.

Additional information

Funding

This work was supported by the UNKP-19-3-SZTE-26 New National Excellence Program of the Ministry for Innovation and Technology, Campus Mundi Program of Tempus Foundation (EFOP-3.4.2-VEKOP-15-2015-00001) and by the project entitled Topical nanodelivery systems funded by the University of Zagreb (Z169).