Traore Yannick Leandre, Chen Yufei, Bernier Anne-Marie, Ho Emmanuel A
Laboratory for Drug Delivery and Biomaterials, College of Pharmacy, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
Department of Biological Sciences, Faculty of Science, Université de Saint-Boniface, Winnipeg, Manitoba, Canada.
Antimicrob Agents Chemother. 2015 Dec;59(12):7680-6. doi: 10.1128/AAC.01819-15. Epub 2015 Sep 28.
The use of polymeric devices for controlled sustained delivery of drugs is a promising approach for the prevention of HIV-1 infection. Unfortunately, certain microbicides, when topically applied vaginally, may be cytotoxic to vaginal epithelial cells and the protective microflora present within the female genital tract. In this study, we evaluated the impact of hydroxychloroquine (HCQ)-loaded, reservoir-type, polyurethane intravaginal rings (IVRs) on the growth of Lactobacillus crispatus and Lactobacillus jensenii and on the viability of vaginal and ectocervical epithelial cells. The IVRs were fabricated using hot-melt injection molding and were capable of providing controlled release of HCQ for 24 days, with mean daily release rates of 17.01 ± 3.6 μg/ml in sodium acetate buffer (pH 4) and 29.45 ± 4.84 μg/ml in MRS broth (pH 6.2). Drug-free IVRs and the released HCQ had no significant effects on bacterial growth or the viability of vaginal or ectocervical epithelial cells. Furthermore, there was no significant impact on the integrity of vaginal epithelial cell monolayers, in comparison with controls, as measured by transepithelial electrical resistance. Overall, this is the first study to evaluate the effects of HCQ-loaded IVRs on the growth of vaginal flora and the integrity of vaginal epithelial cell monolayers.
使用聚合物装置进行药物的控释持续给药是预防HIV-1感染的一种有前景的方法。不幸的是,某些局部阴道应用的杀微生物剂可能对阴道上皮细胞以及女性生殖道内存在的保护性微生物群具有细胞毒性。在本研究中,我们评估了载有羟氯喹(HCQ)的储库型聚氨酯阴道环(IVR)对卷曲乳杆菌和詹氏乳杆菌生长以及阴道和子宫颈外上皮细胞活力的影响。这些IVR采用热熔注射成型法制造,能够在24天内实现HCQ的控释,在醋酸钠缓冲液(pH 4)中的平均每日释放率为17.01±3.6μg/ml,在MRS肉汤(pH 6.2)中的平均每日释放率为29.45±4.84μg/ml。不含药物的IVR和释放出的HCQ对细菌生长或阴道或子宫颈外上皮细胞的活力没有显著影响。此外,与对照组相比,通过跨上皮电阻测量,对阴道上皮细胞单层的完整性没有显著影响。总体而言,这是第一项评估载有HCQ的IVR对阴道菌群生长和阴道上皮细胞单层完整性影响的研究。