pH-responsive nanoparticles releasing tenofovir intended for the prevention of HIV transmission.
pH-responsive nanoparticles releasing tenofovir intended for the prevention of HIV transmission.
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DOI：
10.1016/j.ejpb.2011.06.007
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发表时间：
2011-11
期刊：
影响因子：
--
通讯作者：
Youan BB
中科院分区：
文献类型：
--
作者：
Zhang T;Sturgis TF;Youan BB
本研究旨在验证这样一种假设，即由聚乳酸-乙醇酸共聚物(PLGA)和甲基丙烯酸共聚物(Eudradit®S-100或S-100)共混制得的富马酸替诺福韦奥替诺福韦异丙酯纳米粒(NPs)无细胞毒性，在人精液存在下表现出显著的pH响应释放。采用乳化扩散法制备纳米粒，通过动态光散射法、分光光度法、透射电子显微镜、细胞存活率/跨皮细胞电阻测定等方法对纳米粒的粒径、包封率、释药特性、形态及细胞毒性等进行了表征。通过荧光光谱和共聚焦显微镜观察细胞摄取情况。纳米粒的平均粒径为250 nm，最大EE%分别为16.1%和37.2%。在模拟精液存在下，药物释放率由75%的S-100提高到4倍以上72小时。在浓度达10 mg/ml时，PLGA/S-100纳米粒对阴道内/上皮细胞和皱纹乳杆菌无细胞毒性作用48小时。24小时内颗粒摄取率约为50%。这些阴道细胞系大多通过小窝蛋白介导的途径发生。这些数据表明，使用PLGA/S-100纳米粒作为一种替代的受控给药系统，经阴道给药是一种抗艾滋病毒/艾滋病杀菌剂的前景。
This study is designed to test the hypothesis that Tenofovir(TNF)ortenofovir disoproxil fumarate (TDF) loaded nanoparticles (NPs)prepared with a blend of poly(lactic-co-glycolic acid) (PLGA) and methacrylic acid copolymer (Eudragit® S-100, or S-100)are noncytotoxic and exhibit significant pH-responsive release of anti-HIV microbicides in presence of human semen. After NPs preparation by emulsification diffusion, their size, encapsulation efficiency (EE%), drug release profile, morphology, and cytotoxicity are characterized by dynamic light scattering, spectrophotometry, transmission electron microscopy, and cellular viability assay/transepithelial electrical resistance measurement, respectively. Cellular uptake was elucidated by fluorescence spectroscopy and confocal microscopy. The NP shavean average size of 250 nm, maximal EE% of 16.1% and 37.2% for TNF and TDF, respectively. There is a 4-fold increase in the drug release rate from 75% S-100 blendin the presence of semen fluid simulant over 72 hr. At a concentration up to 10 mg/ml, the PLGA/S-100 NPs are noncytotoxic for 48 hr to vaginal endocervical/epithelial cells and Lactobacillus crispatus. The particle uptake (~50% in 24hr.) by these vaginal cell lines mostly occurred through caveolin-mediated pathway. These data suggest the promise of using PLGA/S-100 NP as an alternative controlled drug delivery system in intravaginal delivery of an anti-HIV/AIDS microbicide.
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