Microemulsions Containing Medium-Chain Glycerides as Transdermal Delivery Systems for Hydrophilic and Hydrophobic Drugs
Microemulsions Containing Medium-Chain Glycerides as Transdermal Delivery Systems for Hydrophilic and Hydrophobic Drugs
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DOI：
10.1208/s12249-009-9251-0
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发表时间：
2009-06-01
影响因子：
3.3
通讯作者：
Lopes, Luciana B.
中科院分区：
文献类型：
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作者：
Hosmer, Jaclyn;Reed, Rachel;Lopes, Luciana B.
我们评估了含有中链甘油酯作为渗透促进剂的微乳液增加亲脂性（孕酮）和亲水性（腺苷）模型药物的经皮递送的能力，以及表面活性剂混合物浓度增加对药物经皮递送的影响。微乳组成的聚山梨酯80，中链甘油酯，和丙二醇（1：1：1，w/w/w）作为表面活性剂的混合物，myvacet油作为油相，和水的开发。选择含有不同浓度的表面活性剂共混物但相似的水/油比的两种微乳液; ME-lo含有比ME-hi更小浓度的表面活性剂（47：20：33和63：14：23表面活性剂/油/水，w/w/w）。虽然在体外孕酮和腺苷释放从ME-lo和ME-hi是相似的，它们的透皮给药受到不同的影响。与孕酮油溶液（0.05 +/-0.01 μ g/cm（2）/h）或腺苷水溶液（在受体相中未检测到药物）相比，ME-lo显著增加了孕酮和腺苷通过猪耳皮肤的通量（4倍或更高，p < 0.05）。通过ME-hi，腺苷的透皮通量而不是孕酮的透皮通量进一步增加（2倍），这表明表面活性剂浓度的增加代表了增强亲水性化合物而不是亲脂性化合物的透皮递送的有趣策略。在培养的成纤维细胞中评估微乳液的相对安全性。在相同浓度（高达50 μ g/mL）下，ME-lo和ME-hi的细胞毒性显着小于十二烷基硫酸钠（被认为是中度至重度刺激物），但与丙二醇（被认为是安全的）相似，表明这些制剂的安全性。
We evaluated the ability of microemulsions containing medium-chain glycerides as penetration enhancers to increase the transdermal delivery of lipophilic (progesterone) and hydrophilic (adenosine) model drugs as well as the effects of an increase in surfactant blend concentration on drug transdermal delivery. Microemulsions composed of polysorbate 80, medium-chain glycerides, and propylene glycol (1:1:1, w/w/w) as surfactant blend, myvacet oil as the oily phase, and water were developed. Two microemulsions containing different concentrations of surfactant blend but similar water/oil ratios were chosen; ME-lo contained a smaller concentration of surfactant than ME-hi (47:20:33 and 63:14:23 surfactant/oil/water, w/w/w). Although in vitro progesterone and adenosine release from ME-lo and ME-hi was similar, their transdermal delivery was differently affected. ME-lo significantly increased the flux of progesterone and adenosine delivered across porcine ear skin (4-fold or higher, p < 0.05) compared to progesterone solution in oil (0.05 +/- 0.01 mu g/cm(2)/h) or adenosine in water (no drug was detected in the receptor phase). The transdermal flux of adenosine, but not of progesterone, was further increased (2-fold) by ME-hi, suggesting that increases in surfactant concentration represent an interesting strategy to enhance transdermal delivery of hydrophilic, but not of lipophilic, compounds. The relative safety of the microemulsions was assessed in cultured fibroblasts. The cytotoxicity of ME-lo and ME-hi was significantly smaller than sodium lauryl sulfate (considered moderate-to-severe irritant) at same concentrations (up to 50 mu g/mL), but similar to propylene glycol (regarded as safe), suggesting the safety of these formulations.