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

Authors Bíró T, Bocsik A, Jurišić Dukovski B, Gróf I, Lovrić J, Csóka I, Deli MA, Aigner Z

Received 5 June 2020

Accepted for publication 18 November 2020

Published 3 February 2021 Volume 2021:15 Pages 351—360

DOI https://doi.org/10.2147/DDDT.S264745

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Professor Manfred Ogris


Tivadar Bíró,1 Alexandra Bocsik,2 Bisera Jurišić Dukovski,3 Ilona Gróf,2,4 Jasmina Lovrić,3 Ildikó Csóka,1 Mária A Deli,2 Zoltán Aigner1

1Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Szeged, Hungary; 2Institute of Biophysics, Biological Research Centre,, Szeged, Hungary; 3Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia; 4Doctoral School of Biology, University of Szeged, Szeged, Hungary

Correspondence: Zoltán Aigner
Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, 6 Eötvös Street, Szeged, H-6720, Hungary
Tel +3662545577
Email aigner.zoltan@szte.hu

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

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