期刊
COLLOIDS AND SURFACES B-BIOINTERFACES
卷 41, 期 1, 页码 25-32出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.colsurfb.2004.09.008
关键词
transdermal drug delivery; AOT; microemulsion; 5-fluorouracil; ATR-FTIR
In vitro transdermal permeation of 5-fluorouracil (antineoplastic), a hydrophilic drug encapsulated in AOT/water/isopropylmyristate water-in-oil microemulsions (MEs), were studied using a modified Keshary and Chien diffusion cell. AOT (aerosol-OT or sodium bis(2-ethylhexyl) sulfosuccinate) is an anionic surfactant, which forms 'water-in-oil' ME in non-aqueous medium. The effect of water and AOT concentrations in MEs to the transdermal permeation of 5-fluorouracil through hairless mouse skin was investigated. MEs with 5:95 weight ratio of AOT:isopropylmyristate, containing 0.9, 1.8, 2.7 and 3.6% w/w of water have showed 1.68-, 2.36-, 3.58- and 3.77-fold increases in the skin flux of 5-fluorouracil (5-FU) respectively, compared to the aqueous solution of drug. The MEs with 5:95, 9:91 and 13:87 weight ratio of AOT:isopropyl myristate at fixed water content W-0 = 15 (W-0 = [H2O]/AOT]) gave 3.58-, 5.04- and 6.3-fold enhancement of drug. In addition, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy was used to examine the effect of ME on lipid alkyl chain, hydration level, and corneocyte cells of the stratum corneum (SC). Results reveal that the ME interacts with a component of the SC and perturbs its architectural structure. The extent of perturbation in the SC depends on the concentration of water and AOT in the ME. Preliminary dermal toxicity studies indicate that the AOT/water/isopropylmyristate ME be safe for the transdermal permeation of 5-FU. (C) 2004 Elsevier B.V. All rights reserved.
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