Abstract：
Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/ AIDS) and unplanned pregnancy affect female reproductive health globally. A single product providing a dual purpose of HIV prophylaxis and contraception may improve adherence to the therapy. Thus, we formulated a female-centric multipurpose prevention technology (MPT) comprising of nanoparticle loaded vaginal gel formulation acting as a contraceptive and microbicide. Eudragit® S100 nanoparticles of Atazanavir sulphate (ATZ; antiviral) and Fluoxetine hydrochloride (FLX; repurposed spermicide) were prepared for pH dependent drug release and loaded in carrageenan and HPMC K200M gel. The particle size of ATZ and FLX nanoparticles was 396.7 ± 20.64 nm and 226.5 ± 2.08 nm respectively. The in vitro release of the gel formulation in simulated seminal fluid (pH 7.6) showed 96.16% and 95.98% release of ATZ and FLX respectively at the end of 8 h. The in vitro anti-HIV and spermicidal activity of the formulation was above 80% for low drug concentrations. In vivo studies on murine model showed no signs of inflammation or vaginal epithelial injury. Curcumin based imaging confirmed the retention of the formulation in the reproductive tract of mice with minimal leakage. Nanoparticles in gel enabled non-invasive and localised delivery with minimal side effects and can be an effective prophylactic therapy.
摘要：
人体免疫机能丧失病毒/后天免疫机能丧失综合症(艾滋病毒/艾滋病)和意外怀孕影响全球女性生殖健康。提供避孕和HIV预防的双重目的的单一产品可以改善对治疗的依从性。因此，我们制定了一种以女性为中心的多用途预防技术（MPT），该技术由纳米颗粒阴道凝胶制剂作为避孕药和杀微生物剂。制备阿扎那韦硫酸盐(ATZ;抗病毒剂)和盐酸氟西汀(FLX;再利用的杀精子剂)的Eudragit®S100纳米颗粒用于pH依赖性药物释放,并装载在角叉菜胶和HPMCK200M凝胶中。ATZ和FLX纳米颗粒的粒径分别为396.7±20.64nm和226.5±2.08nm。凝胶制剂在模拟精液(pH7.6)中的体外释放在8小时结束时分别显示出96.16%和95.98%的ATZ和FLX释放。对于低药物浓度,制剂的体外抗HIV和杀精子活性高于80%。对鼠模型的体内研究显示没有炎症或阴道上皮损伤的迹象。基于姜黄素的成像证实制剂在小鼠生殖道中的保留具有最小的渗漏。凝胶中的纳米颗粒实现了具有最小副作用的非侵入性和局部递送,并且可以是有效的预防性疗法。
