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dc.creatorDobričić, Vladimir
dc.creatorNikolić, Katarina
dc.creatorVladimirov, Sote
dc.creatorČudina, Olivera
dc.date.accessioned2019-09-02T11:42:31Z
dc.date.available2019-09-02T11:42:31Z
dc.date.issued2014
dc.identifier.issn0928-0987
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/2235
dc.description.abstractIn this paper, human skin and corneal permeability of twenty-two newly synthesized 17 beta-carboxamide steroids was predicted using biopartitioning micellar chromatography (BMC). These compounds are potential soft glucocorticoids with local anti-inflammatory activity when applied to the skin or eye. BMC systems are used to simulate physicochemical properties of human skin (BMC-skin) and cornea (BMC-cornea). Micellar mobile phase, consisted of 0.04 M solution of polyoxyethylene (23) lauryl ether (Brij 35), was prepared at different pH values - 5.50 (BMC-skin) and 7.50 (BMC-cornea). Retention factors (k), obtained by use of BMC, were calculated for all newly synthesized 17 beta-carboxamide steroids as well as for parent glucocorticoids (hydrocortisone, prednisolone, methylprednisolone, dexamethasone and betamethasone). Good correlation was obtained between BMC-skin retention factors and permeability coefficients calculated by use of the artificial membrane that simulates stratum corneum of the human skin. Quantitative structure-retention relationship (QSRR) study was performed in order to explain retention factors of these compounds in the tested BMC systems. ANN-QSRR(k), PLS-QSRR(k) and MLR-QSRR(k) models, created by use of BMC-skin retention data, were compared and optimal model (PLS-QSRR(k)) was selected. Molecular descriptors of the selected model indicate that lipophilicity and number of short C C fragments of tested compounds have the strongest influence on the retention in the BMC-skin system and presumably on their in vivo permeability through human skin. The same model can be applied to the BMC-cornea system and the same conclusion can be drawn for corneal permeability. This model could be used as a predictive tool for the synthesis of novel 17 beta-carboxamide steroids with desirable permeability through human skin or cornea, depending on their potential pharmacological application.en
dc.publisherElsevier Science BV, Amsterdam
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172041/RS//
dc.rightsrestrictedAccess
dc.sourceEuropean Journal of Pharmaceutical Sciences
dc.subjectSoft glucocorticoidsen
dc.subjectBiopartitioning micellar chromatographyen
dc.subjectSkin and corneal permeability predictionen
dc.subjectQuantitative structure-retentionen
dc.subjectrelationshipen
dc.titleBiopartitioning micellar chromatography as a predictive tool for skin and corneal permeability of newly synthesized 17 beta-carboxamide steroidsen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractВладимиров, Соте; Николић, Катарина; Чудина, Оливера; Добричић, Владимир;
dc.citation.volume56
dc.citation.spage105
dc.citation.epage112
dc.citation.other56: 105-112
dc.citation.rankM21
dc.identifier.wos000335872700011
dc.identifier.doi10.1016/j.ejps.2014.02.007
dc.identifier.pmid24607748
dc.identifier.scopus2-s2.0-84896534897
dc.identifier.rcubconv_3087
dc.type.versionpublishedVersion


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