Biopartitioning micellar chromatography as a predictive tool for skin and corneal permeability of newly synthesized 17 beta-carboxamide steroids
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2014
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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.
Ključne reči:
Soft glucocorticoids / Biopartitioning micellar chromatography / Skin and corneal permeability prediction / Quantitative structure-retention / relationshipIzvor:
European Journal of Pharmaceutical Sciences, 2014, 56, 105-112Izdavač:
- Elsevier Science BV, Amsterdam
Finansiranje / projekti:
DOI: 10.1016/j.ejps.2014.02.007
ISSN: 0928-0987
PubMed: 24607748
WoS: 000335872700011
Scopus: 2-s2.0-84896534897
Institucija/grupa
PharmacyTY - JOUR AU - Dobričić, Vladimir AU - Nikolić, Katarina AU - Vladimirov, Sote AU - Čudina, Olivera PY - 2014 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2235 AB - 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. PB - Elsevier Science BV, Amsterdam T2 - European Journal of Pharmaceutical Sciences T1 - Biopartitioning micellar chromatography as a predictive tool for skin and corneal permeability of newly synthesized 17 beta-carboxamide steroids VL - 56 SP - 105 EP - 112 DO - 10.1016/j.ejps.2014.02.007 ER -
@article{ author = "Dobričić, Vladimir and Nikolić, Katarina and Vladimirov, Sote and Čudina, Olivera", year = "2014", 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.", publisher = "Elsevier Science BV, Amsterdam", journal = "European Journal of Pharmaceutical Sciences", title = "Biopartitioning micellar chromatography as a predictive tool for skin and corneal permeability of newly synthesized 17 beta-carboxamide steroids", volume = "56", pages = "105-112", doi = "10.1016/j.ejps.2014.02.007" }
Dobričić, V., Nikolić, K., Vladimirov, S.,& Čudina, O.. (2014). Biopartitioning micellar chromatography as a predictive tool for skin and corneal permeability of newly synthesized 17 beta-carboxamide steroids. in European Journal of Pharmaceutical Sciences Elsevier Science BV, Amsterdam., 56, 105-112. https://doi.org/10.1016/j.ejps.2014.02.007
Dobričić V, Nikolić K, Vladimirov S, Čudina O. Biopartitioning micellar chromatography as a predictive tool for skin and corneal permeability of newly synthesized 17 beta-carboxamide steroids. in European Journal of Pharmaceutical Sciences. 2014;56:105-112. doi:10.1016/j.ejps.2014.02.007 .
Dobričić, Vladimir, Nikolić, Katarina, Vladimirov, Sote, Čudina, Olivera, "Biopartitioning micellar chromatography as a predictive tool for skin and corneal permeability of newly synthesized 17 beta-carboxamide steroids" in European Journal of Pharmaceutical Sciences, 56 (2014):105-112, https://doi.org/10.1016/j.ejps.2014.02.007 . .