Design of ocular drug delivery platforms and in vitro - in vivo evaluation of riboflavin to the cornea by non-interventional (epi-on) technique for keratoconus treatment

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dc.authoridOzturk, Naile / 0000-0002-7617-8433
dc.authoridCAKMAK, HASAN BASRI / 0000-0001-6877-8773
dc.authorwosidPOLAT, Hilal KOC / AAA-7672-2021
dc.authorwosidOzturk, Naile / F-3650-2017
dc.contributor.authorAytekin, Eren
dc.contributor.authorOzturk, Naile
dc.contributor.authorVurla, Imran
dc.contributor.authorPolat, H. Kerem
dc.contributor.authorCakmak, Hasan Basri
dc.contributor.authorCalis, Sema
dc.contributor.authorPehlivan, Sibel Bozdag
dc.date.accessioned2021-11-01T15:05:06Z
dc.date.available2021-11-01T15:05:06Z
dc.date.issued2020
dc.department[Belirlenecek]
dc.description.abstractAim: Keratoconus is a common and progressive eye disease characterized by thinning and tapering of the cornea. This degenerative eye disease is currently treated in the clinic with an interventional technique (epi-off) that can cause serious side effects as a result of the surgical procedure. The aim of this project is to design innovative formulations for the development of a riboflavin-containing medicinal product to develop a non-invasive (epi-on) keratoconus treatment as an alternative to current treatment modalities. Methods: Nanostructured lipid carriers (NLCs) were successfully loaded with either riboflavin base of riboflavin-5-phosphate sodium and designed with either Stearylamine (positive charge) or Trancutol P (permeation enhancer). In vitro characterization studies, cytotoxicity and permeability studies were performed. Selected formulations and commercial preparations were applied and compared in ex-vivo corneal drug accumulation and transition studies. Furthermore, in vivo studies were performed to assess drug accumulation in the rat cornea and the corneal stability after NLC treatment was investigated via a biomechanical study on isolated rabbit corneas. Results: Both in vitro and ex-vivo as well as in vivo data showed that from the prepared NLC formulations, the most effective formulation was riboflavin-5-phosphate sodium containing NLC with Transcutol P as permeation enhancer. It possessed the highest drug loading content, low accumulation in the cornea but high permeability through the cornea as well as the highest functional performance in corneal crosslinking. Conclusion: Topical application of riboflavin-5-phosphate sodium loaded NLC systems designed with permeation enhancer Transcutol P may act as a potential alternative for non-invasive keratoconus treatments.
dc.description.sponsorshipTUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [215S685]en_US
dc.description.sponsorshipThe authors would like to thank Gattefosse and IOI Chemicals for their kind supports. This research was financially supported by TUBITAK, (Research Project 215S685).en_US
dc.identifier.doi10.1016/j.jconrel.2020.05.017
dc.identifier.endpage249en_US
dc.identifier.issn0168-3659
dc.identifier.issn1873-4995
dc.identifier.pmid32413453
dc.identifier.scopus2-s2.0-85084940581
dc.identifier.scopusqualityQ1
dc.identifier.startpage238en_US
dc.identifier.urihttps://doi.org/10.1016/j.jconrel.2020.05.017
dc.identifier.urihttps://hdl.handle.net/11491/7110
dc.identifier.volume324en_US
dc.identifier.wosWOS:000558613300003
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthor[Belirlenecek]
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofJournal Of Controlled Release
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectKeratoconusen_US
dc.subjectEpi-onen_US
dc.subjectRiboflavinen_US
dc.subjectRiboflavin-5-phosphate sodiumen_US
dc.subjectDrug deliveryen_US
dc.subjectNanostructured lipid carrieren_US
dc.titleDesign of ocular drug delivery platforms and in vitro - in vivo evaluation of riboflavin to the cornea by non-interventional (epi-on) technique for keratoconus treatment
dc.typeArticle

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