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.
TY - 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 . .
