Development and Evaluation of an In Vitro Vaginal Model for Assessment of Drug's Biopharmaceutical Properties: Curcumin
Development and Evaluation of an In Vitro Vaginal Model for Assessment of Drug's Biopharmaceutical Properties: Curcumin
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DOI：
10.1208/s12249-012-9837-9
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发表时间：
2012-12-01
影响因子：
3.3
通讯作者：
Kristl, Albin
中科院分区：
文献类型：
--
作者：
Berginc, Katja;Skalko-Basnet, Natasa;Kristl, Albin
当肠道药物吸收受到有问题的生物制药药物性质的阻碍时，阴道给药是经口途径在实现全身或局部治疗效果方面有前途的替代方案。本研究的目的是建立一个体外阴道模型，并使用它来表征脂质体相关的姜黄素的生物制药特性，用于阴道输送。在牛阴道粘膜上评估了高/低渗透性化合物的体外渗透性、代谢和组织保留，并与通过Caco-2细胞和大鼠空肠测定的体外渗透性进行了比较。结果表明，肠粘膜在根据药物的渗透性将其分为高/低渗透性类别方面优于阴道粘膜上级。被动扩散被认为是药物透过阴道粘膜的主要机制，并且不受转运蛋白-酶联盟的影响，因为与肠道相比，它们的表达/活性显著降低。来自溶液形式的姜黄素渗透性是所有测试物质中最低的，这是由于其显著的组织保留和姜黄素-粘液相互作用。脂质体相关的姜黄素的渗透性甚至更低，但脂质体相关的姜黄素与阴道组织的结合显著更高。脂质体姜黄素的渗透性和组织滞留具有囊泡大小依赖性。脂质体结合的姜黄素的阴道应用在阴道组织中提供相对高水平的姜黄素，具有有限的全身吸收。
Vaginal administration is a promising alternative to the per-oral route in achieving systemic or local therapeutic effects, when intestinal drug absorption is hindered by problematic biopharmaceutical drug properties. The aim of this study was to establish an in vitro vaginal model and use it to characterize biopharmaceutical properties of liposomally associated curcumin destined for vaginal delivery. The in vitro permeability, metabolism, and tissue retention of high/low permeable compounds were assessed on cow vaginal mucosa and compared to the permeabilities determined through Caco-2 cells and rat jejunum in vitro. The results showed that the intestinal mucosa was superior to the vaginal one in categorizing drugs based on their permeabilities in high/low permeable classes. Passive diffusion was found to be the main mechanism of drug penetration through vaginal mucosa and it was not affected by transporter-enzyme alliance, as their expression/activity was significantly reduced compared to the intestinal tract. Curcumin permeability from the solution form was the lowest of all tested substances due to its significant tissue retention and curcumin-mucus interactions. The permeability of liposomally associated curcumin was even lower but the binding of liposomally associated curcumin to the vaginal tissue was significantly higher. The permeability and tissue retention of liposomal curcumin were vesicle size dependent. Vaginal application of liposomally associated curcumin provides relatively high levels of curcumin in vaginal tissue, with limited systemic absorption.