Comparative biophysical properties of tenofovir-loaded, thiolated and nonthiolated chitosan nanoparticles intended for HIV prevention.
Comparative biophysical properties of tenofovir-loaded, thiolated and nonthiolated chitosan nanoparticles intended for HIV prevention.
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DOI：
10.2217/nnm.13.136
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发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Youan BB
中科院分区：
文献类型：
--
作者：
Meng J;Zhang T;Agrahari V;Ezoulin MJ;Youan BB
本研究旨在验证以下假设：与天然CS纳米粒相比，载替诺福韦(一种抗HIV微生物剂)壳聚糖-硫代乙醇酸共轭(CS-TGA)纳米粒(NPs)具有更好的粘附性。纳米粒子是通过离子致凝胶法制备的。采用动态光散射法和紫外法分别分析了微球的平均粒径、包封率和释药特性。用比色法/荧光法测定其对VK2/E6E7和End1/E6E7细胞的细胞毒性、细胞摄取和摄取机制，并用猪阴道组织测定粘附率。优化后的纳米粒平均粒径为240~252 nm，最大包封率为22.60%。替诺福韦在CS和CS-TGA纳米粒中的释放分别符合一级模型和Higuchi模型。这两种纳米粒在48小时内都没有细胞毒性。细胞摄取主要通过小窝蛋白介导的途径进行，这种摄取具有时间依赖性。CS-TGA纳米粒的粘附率是CS纳米粒的5倍，2小时后达到65%。总的来说，CS-TGA纳米粒具有优异的生物物理性能，并有可能最大限度地延长用于预防HIV传播的局部杀菌剂(如替诺福韦)的保留时间。
This study is designed to test the hypothesis that tenofovir-loaded (an anti-HIV microbicide) chitosan–thioglycolic acid-conjugated (CS–TGA) nanoparticles (NPs) exhibit superior biophysical properties for mucoadhesion compared with those of native CS NPs. The NPs are prepared by ionotropic gelation. The particle mean diameter, encapsulation efficiency and release profile are analyzed by dynamic light scattering and UV spectroscopy, respectively. The cytotoxicity, cellular uptake and uptake mechanism are assessed on VK2/E6E7 and End1/E6E7 cell lines by colorimetry/fluorimetry, and percentage mucoadhesion is assessed using porcine vaginal tissue. The mean diameter of the optimal NP formulations ranges from 240 to 252 nm, with a maximal encapsulation efficiency of 22.60%. Tenofovir release from CS and CS–TGA NPs follows first-order and Higuchi models, respectively. Both NPs are noncytotoxic in 48 h. The cellular uptake, which is time dependent, mainly occurs via the caveolin-mediated pathway. The percentage of mucoadhesion of CS–TGA NPs is fivefold higher than that of CS NPs, and reached up to 65% after 2 h. Collectively, CS–TGA NPs exhibit superior biophysical properties and can potentially maximize the retention time of a topical microbicide, such as tenofovir, intended for the prevention of HIV transmission.
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