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Microemulsions as topical delivery vehicles for the anti-melanoma prodrug, temozolomide hexyl ester (TMZA-HE)

Suppasansatorn, Panassaya, Nimmannit, Ubonthip, Conway, Barbara R, Du, Lingran and Wang, Yongfeng (2007) Microemulsions as topical delivery vehicles for the anti-melanoma prodrug, temozolomide hexyl ester (TMZA-HE). Journal of Pharmacy and Pharmacology, 59 (6). pp. 787-794. ISSN 0022-3573

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Abstract

A prodrug, temozolomide acid hexyl ester (TMZA-HE), was identified as a skin-deliverable congener for temozolomide (TMZ) to treat skin cancers. Poor solubility and instability of TMZA-HE rendered a serious challenge for formulation of a topical preparation. Microemulsions (ME) were chosen as a potential vehicle for TMZA-HE topical preparations. ME systems were constructed with either oleic acid (OA) or isopropyl myristate (IPM) as the oil phase and tocopheryl (vitamin E) polyethylene glycol 1000 succinate (VE-TPGS) as a surfactant. Topical formulations of OA and IPM ME systems demonstrated beneficial solubilising ability and provided a stable environment for the prodrug, TMZA-HE. Significant differences between the microstructures of OA and IPM ME systems were revealed by freeze fracture electron microscopy (FFEM) and different loading abilities and permeation potencies between the two systems were also identified. In permeation studies, IPM ME systems, with inclusion of isopropyl alcohol (IPA) as a co-surfactant, significantly increased TMZA-HE permeation through silicon membranes and rat skin resulting in less drug retention within the skin, while OA ME systems demonstrated higher solubilising ability and a higher concentration of TMZA-HE retained within the skin. Therefore IPM ME systems are promising for transdermal delivery of TMZA-HE and OA ME systems may be a suitable choice for a topical formulation of TMZA-HE.

Item Type: Article
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
Schools: School of Applied Sciences
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Depositing User: Sharon Beastall
Date Deposited: 04 Nov 2010 11:50
Last Modified: 04 Nov 2010 11:50
URI: http://eprints.hud.ac.uk/id/eprint/8941

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