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一种阴道给药模型。

A vaginal drug delivery model.

作者信息

Mirza Mohd Aamir, Panda Amulya K, Asif S, Verma Devina, Talegaonkar Sushama, Manzoor Nikhat, Khan Amber, Ahmed Farhan Jalees, Dudeja Mridu, Iqbal Zeenat

机构信息

a Department of Pharmaceutics , Faculty of Pharmacy, Jamia Hamdard , New Delhi , India.

b Product Development Cell , National Institute of Immunology , New Delhi , India.

出版信息

Drug Deliv. 2016 Oct;23(8):3123-3134. doi: 10.3109/10717544.2016.1153749. Epub 2016 Mar 14.

Abstract

Efficient drug delivery at vaginal cavity is often a challenge owing to its peculiar physiological variations including vast differences in pH. Keeping in view this attribute of the target site, the current work was aimed at developing formulation strategies which could overcome this and successfully deliver molecules like itraconazole through SLNs. Optimized SLNs with the given composition was selected for further development into mucoadhesive and thermosensitive gel. Stearic acid and Compritol 888 (1:1, w/w ratio) as lipid, a mixture of 3% Poloxomer 188 and 0.5% sodium taurocholate as surfactant and organic to aqueous ratio of 10:50 was taken. Carbopol 934 and Pluronic F 127 were taken for the development of gel. Optimized gel exhibited a desired gelling temperature (35 °C); viscosity (0.920 PaS) and appreciable in vitro drug release (62.2% in 20 h). MTT assay did not show any cytotoxic effect of the gel. When evaluated in vivo, it did not exhibit any irritation potential despite appreciable bioadhesion. A remarkable decrease in CFUs was also observed in comparison with control and marketed formulation when evaluated in rat infection model. Thus, the proposed study defines the challenges for developing a suitable formulation system overcoming the delivery barriers of the vaginal site.

摘要

由于阴道腔特殊的生理变化,包括pH值差异巨大,在该部位实现高效药物递送往往是一项挑战。鉴于靶部位的这一特性,当前的工作旨在开发能够克服这一问题并通过固体脂质纳米粒成功递送伊曲康唑等分子的制剂策略。选择具有给定组成的优化固体脂质纳米粒进一步开发成粘膜粘附性热敏凝胶。选用硬脂酸和Compritol 888(1:1,重量比)作为脂质,3%泊洛沙姆188和0.5%牛磺胆酸钠的混合物作为表面活性剂,有机相与水相比例为10:50。采用卡波姆934和普朗尼克F127来制备凝胶。优化后的凝胶表现出理想的胶凝温度(35°C)、粘度(0.920 PaS)以及可观的体外药物释放率(20小时内为62.2%)。MTT试验未显示该凝胶有任何细胞毒性作用。在体内评估时,尽管有明显的生物粘附性,但它并未表现出任何刺激潜力。在大鼠感染模型中进行评估时,与对照和市售制剂相比,还观察到菌落形成单位显著减少。因此,本研究明确了开发合适的制剂系统以克服阴道部位递送障碍所面临的挑战。

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