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开发一种用于阴道递送达泊甘油的脂质体杀微生物剂制剂,以预防 HIV。

Development of a liposome microbicide formulation for vaginal delivery of octylglycerol for HIV prevention.

机构信息

Magee Womens Research Institute, Pittsburgh, PA, USA.

出版信息

Drug Dev Ind Pharm. 2012 Aug;38(8):995-1007. doi: 10.3109/03639045.2011.637048. Epub 2011 Dec 10.

Abstract

The feasibility of using a liposome drug delivery system to formulate octylglycerol (OG) as a vaginal microbicide product was explored. A liposome formulation was developed containing 1% OG and phosphatidyl choline in a ratio that demonstrated in vitro activity against Neisseria gonorrhoeae, HSV-1, HSV-2 and HIV-1 while sparing the innate vaginal flora, Lactobacillus. Two conventional gel formulations were prepared for comparison. The OG liposome formulation with the appropriate OG/lipid ratio and dosing level had greater efficacy than either conventional gel formulation and maintained this efficacy for at least 2 months. No toxicity was observed for the liposome formulation in ex vivo testing in a human ectocervical tissue model or in vivo testing in the macaque safety model. Furthermore, minimal toxicity was observed to lactobacilli in vitro or in vivo safety testing. The OG liposome formulation offers a promising microbicide product with efficacy against HSV, HIV and N. gonorrhoeae.

摘要

探讨了使用脂质体药物传递系统将辛基甘油(OG)制成阴道杀微生物剂产品的可行性。开发了一种脂质体配方,其中含有 1%的 OG 和磷脂酰胆碱,其比例在体外对淋病奈瑟菌、单纯疱疹病毒 1 型、单纯疱疹病毒 2 型和 HIV-1 具有活性,同时保留了阴道固有菌群乳杆菌。还制备了两种常规凝胶制剂进行比较。具有适当 OG/脂质比例和剂量水平的 OG 脂质体配方比任何一种常规凝胶制剂都更有效,并且至少能维持 2 个月的功效。在人宫颈外植体模型的体外试验或猕猴安全模型的体内试验中,均未观察到脂质体配方的毒性。此外,在体外或体内安全性试验中,对乳杆菌的毒性也很小。OG 脂质体配方为具有抗单纯疱疹病毒、艾滋病毒和淋病奈瑟菌功效的杀微生物剂产品提供了一个有希望的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3900/4460795/f0c10c6cd721/nihms-691215-f0001.jpg

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