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A PAMPA Assay as Fast Predictive Model of Passive Human Skin Permeability of New Synthesized Corticosteroid C-21 Esters

The permeation properties of twenty newly synthesized α-alkoxyalkanoyl and α-aryloxyalkanoyl C-21 esters of standard corticosteroids: Fluocinolone acetonide, dexamethasone, triamcinolone acetonide and hydrocortisone were established using a PAMPA assay (70% silicone oil and 30% isopropyl myristate)....

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Autores principales: Markovic, Bojan D., Vladimirov, Sote M., Cudina, Olivera A., Odovic, Jadranka V., Karljikovic-Rajic, Katarina D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268546/
https://www.ncbi.nlm.nih.gov/pubmed/22222907
http://dx.doi.org/10.3390/molecules17010480
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author Markovic, Bojan D.
Vladimirov, Sote M.
Cudina, Olivera A.
Odovic, Jadranka V.
Karljikovic-Rajic, Katarina D.
author_facet Markovic, Bojan D.
Vladimirov, Sote M.
Cudina, Olivera A.
Odovic, Jadranka V.
Karljikovic-Rajic, Katarina D.
author_sort Markovic, Bojan D.
collection PubMed
description The permeation properties of twenty newly synthesized α-alkoxyalkanoyl and α-aryloxyalkanoyl C-21 esters of standard corticosteroids: Fluocinolone acetonide, dexamethasone, triamcinolone acetonide and hydrocortisone were established using a PAMPA assay (70% silicone oil and 30% isopropyl myristate). The data were compared with parent corticosteroids with addition of mometasone furoate and hydrocortisone acetate. All newly synthesized corticosteroid C-21 esters have effective permeability coefficients higher then -6, mostly followed with high values of retention factors and low permeation. The examined compounds were grouped through relationship between obtained retention factors and permeation parameters (groups I–III). The classification confirmed group I (membrane retentions as well as permeation lower then 30%) for all corticosteroid standards except mometasone furoate, a potent topical corticosteroid which, with high membrane retention (81%) and low permeation (7.7%) fits into group III. The largest number of new synthesized corticosteroids C-21 esters, among them all fluocinolone acetonide C-21 esters, have high membrane retentions (32.4%–86.5%) and low permeations (1.3%–27.1%), fitting in group III. The classification was related to previously obtained anti-inflammatory activity data for the fluocinolone acetonide C-21 esters series. According to the PAMPA results the new synthesized esters could be considered as potential new prodrugs with useful benefit/risk ratio.
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spelling pubmed-62685462018-12-11 A PAMPA Assay as Fast Predictive Model of Passive Human Skin Permeability of New Synthesized Corticosteroid C-21 Esters Markovic, Bojan D. Vladimirov, Sote M. Cudina, Olivera A. Odovic, Jadranka V. Karljikovic-Rajic, Katarina D. Molecules Article The permeation properties of twenty newly synthesized α-alkoxyalkanoyl and α-aryloxyalkanoyl C-21 esters of standard corticosteroids: Fluocinolone acetonide, dexamethasone, triamcinolone acetonide and hydrocortisone were established using a PAMPA assay (70% silicone oil and 30% isopropyl myristate). The data were compared with parent corticosteroids with addition of mometasone furoate and hydrocortisone acetate. All newly synthesized corticosteroid C-21 esters have effective permeability coefficients higher then -6, mostly followed with high values of retention factors and low permeation. The examined compounds were grouped through relationship between obtained retention factors and permeation parameters (groups I–III). The classification confirmed group I (membrane retentions as well as permeation lower then 30%) for all corticosteroid standards except mometasone furoate, a potent topical corticosteroid which, with high membrane retention (81%) and low permeation (7.7%) fits into group III. The largest number of new synthesized corticosteroids C-21 esters, among them all fluocinolone acetonide C-21 esters, have high membrane retentions (32.4%–86.5%) and low permeations (1.3%–27.1%), fitting in group III. The classification was related to previously obtained anti-inflammatory activity data for the fluocinolone acetonide C-21 esters series. According to the PAMPA results the new synthesized esters could be considered as potential new prodrugs with useful benefit/risk ratio. MDPI 2012-01-05 /pmc/articles/PMC6268546/ /pubmed/22222907 http://dx.doi.org/10.3390/molecules17010480 Text en © 2012 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Markovic, Bojan D.
Vladimirov, Sote M.
Cudina, Olivera A.
Odovic, Jadranka V.
Karljikovic-Rajic, Katarina D.
A PAMPA Assay as Fast Predictive Model of Passive Human Skin Permeability of New Synthesized Corticosteroid C-21 Esters
title A PAMPA Assay as Fast Predictive Model of Passive Human Skin Permeability of New Synthesized Corticosteroid C-21 Esters
title_full A PAMPA Assay as Fast Predictive Model of Passive Human Skin Permeability of New Synthesized Corticosteroid C-21 Esters
title_fullStr A PAMPA Assay as Fast Predictive Model of Passive Human Skin Permeability of New Synthesized Corticosteroid C-21 Esters
title_full_unstemmed A PAMPA Assay as Fast Predictive Model of Passive Human Skin Permeability of New Synthesized Corticosteroid C-21 Esters
title_short A PAMPA Assay as Fast Predictive Model of Passive Human Skin Permeability of New Synthesized Corticosteroid C-21 Esters
title_sort pampa assay as fast predictive model of passive human skin permeability of new synthesized corticosteroid c-21 esters
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268546/
https://www.ncbi.nlm.nih.gov/pubmed/22222907
http://dx.doi.org/10.3390/molecules17010480
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