Molecules 2012, 17(1), 480-491; doi:10.3390/molecules17010480
Article

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

Received: 15 December 2011; in revised form: 29 December 2011 / Accepted: 30 December 2011 / Published: 5 January 2012
(This article belongs to the Section Medicinal Chemistry)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: 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.
Keywords: corticosteroid C-21 esters; prodrug; PAMPA; membrane retention; permeation parameter
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MDPI and ACS Style

Markovic, B.D.; Vladimirov, S.M.; Cudina, O.A.; Odovic, J.V.; Karljikovic-Rajic, K.D. A PAMPA Assay as Fast Predictive Model of Passive Human Skin Permeability of New Synthesized Corticosteroid C-21 Esters. Molecules 2012, 17, 480-491.

AMA Style

Markovic BD, Vladimirov SM, Cudina OA, Odovic JV, Karljikovic-Rajic KD. A PAMPA Assay as Fast Predictive Model of Passive Human Skin Permeability of New Synthesized Corticosteroid C-21 Esters. Molecules. 2012; 17(1):480-491.

Chicago/Turabian Style

Markovic, Bojan D.; Vladimirov, Sote M.; Cudina, Olivera A.; Odovic, Jadranka V.; Karljikovic-Rajic, Katarina D. 2012. "A PAMPA Assay as Fast Predictive Model of Passive Human Skin Permeability of New Synthesized Corticosteroid C-21 Esters." Molecules 17, no. 1: 480-491.

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