New Approach in Ocular Drug Delivery: In vitro and ex vivo Investigation of Cyclodextrin-Containing, Mucoadhesive Eye Drop Formulations
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...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2021-02-01
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| Series: | Drug Design, Development and Therapy |
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| Online Access: | https://www.dovepress.com/new-approach-in-ocular-drug-delivery-in-vitro-and-ex-vivo-investigatio-peer-reviewed-article-DDDT |
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| author | Bíró T Bocsik A Jurišić Dukovski B Gróf I Lovrić J Csóka I Deli MA Aigner Z |
| author_facet | Bíró T Bocsik A Jurišić Dukovski B Gróf I Lovrić J Csóka I Deli MA Aigner Z |
| author_sort | Bíró T |
| collection | DOAJ |
| description | 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, HungaryCorrespondence: Zoltán AignerInstitute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, 6 Eötvös Street, Szeged, H-6720, HungaryTel +3662545577Email aigner.zoltan@szte.huBackground: 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 |
| first_indexed | 2024-12-22T17:24:29Z |
| format | Article |
| id | doaj.art-907199ba7ecb41768e33017d5b125ad9 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-22T17:24:29Z |
| publishDate | 2021-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-907199ba7ecb41768e33017d5b125ad92022-12-21T18:18:45ZengDove Medical PressDrug Design, Development and Therapy1177-88812021-02-01Volume 1535136061698New Approach in Ocular Drug Delivery: In vitro and ex vivo Investigation of Cyclodextrin-Containing, Mucoadhesive Eye Drop FormulationsBíró TBocsik AJurišić Dukovski BGróf ILovrić JCsóka IDeli MAAigner ZTivadar 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, HungaryCorrespondence: Zoltán AignerInstitute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, 6 Eötvös Street, Szeged, H-6720, HungaryTel +3662545577Email aigner.zoltan@szte.huBackground: 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 modelhttps://www.dovepress.com/new-approach-in-ocular-drug-delivery-in-vitro-and-ex-vivo-investigatio-peer-reviewed-article-DDDTprednisolonecyclodextrinocular drug deliverymucoadhesionhuman corneal epithelial cell lineex vivo cornea model |
| spellingShingle | Bíró T Bocsik A Jurišić Dukovski B Gróf I Lovrić J Csóka I Deli MA Aigner Z New Approach in Ocular Drug Delivery: In vitro and ex vivo Investigation of Cyclodextrin-Containing, Mucoadhesive Eye Drop Formulations Drug Design, Development and Therapy prednisolone cyclodextrin ocular drug delivery mucoadhesion human corneal epithelial cell line ex vivo cornea model |
| title | New Approach in Ocular Drug Delivery: In vitro and ex vivo Investigation of Cyclodextrin-Containing, Mucoadhesive Eye Drop Formulations |
| title_full | New Approach in Ocular Drug Delivery: In vitro and ex vivo Investigation of Cyclodextrin-Containing, Mucoadhesive Eye Drop Formulations |
| title_fullStr | New Approach in Ocular Drug Delivery: In vitro and ex vivo Investigation of Cyclodextrin-Containing, Mucoadhesive Eye Drop Formulations |
| title_full_unstemmed | New Approach in Ocular Drug Delivery: In vitro and ex vivo Investigation of Cyclodextrin-Containing, Mucoadhesive Eye Drop Formulations |
| title_short | New Approach in Ocular Drug Delivery: In vitro and ex vivo Investigation of Cyclodextrin-Containing, Mucoadhesive Eye Drop Formulations |
| title_sort | new approach in ocular drug delivery in vitro and ex vivo investigation of cyclodextrin containing mucoadhesive eye drop formulations |
| topic | prednisolone cyclodextrin ocular drug delivery mucoadhesion human corneal epithelial cell line ex vivo cornea model |
| url | https://www.dovepress.com/new-approach-in-ocular-drug-delivery-in-vitro-and-ex-vivo-investigatio-peer-reviewed-article-DDDT |
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