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Biopartitioning micellar chromatography as a predictive tool for skin and corneal permeability of newly synthesized 17 beta-carboxamide steroids
dc.creator | Dobričić, Vladimir | |
dc.creator | Nikolić, Katarina | |
dc.creator | Vladimirov, Sote | |
dc.creator | Čudina, Olivera | |
dc.date.accessioned | 2019-09-02T11:42:31Z | |
dc.date.available | 2019-09-02T11:42:31Z | |
dc.date.issued | 2014 | |
dc.identifier.issn | 0928-0987 | |
dc.identifier.uri | https://farfar.pharmacy.bg.ac.rs/handle/123456789/2235 | |
dc.description.abstract | In 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.publisher | Elsevier Science BV, Amsterdam | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172041/RS// | |
dc.rights | restrictedAccess | |
dc.source | European Journal of Pharmaceutical Sciences | |
dc.subject | Soft glucocorticoids | en |
dc.subject | Biopartitioning micellar chromatography | en |
dc.subject | Skin and corneal permeability prediction | en |
dc.subject | Quantitative structure-retention | en |
dc.subject | relationship | en |
dc.title | Biopartitioning micellar chromatography as a predictive tool for skin and corneal permeability of newly synthesized 17 beta-carboxamide steroids | en |
dc.type | article | |
dc.rights.license | ARR | |
dcterms.abstract | Владимиров, Соте; Николић, Катарина; Чудина, Оливера; Добричић, Владимир; | |
dc.citation.volume | 56 | |
dc.citation.spage | 105 | |
dc.citation.epage | 112 | |
dc.citation.other | 56: 105-112 | |
dc.citation.rank | M21 | |
dc.identifier.wos | 000335872700011 | |
dc.identifier.doi | 10.1016/j.ejps.2014.02.007 | |
dc.identifier.pmid | 24607748 | |
dc.identifier.scopus | 2-s2.0-84896534897 | |
dc.type.version | publishedVersion |