Formulation of Tenofovir-Loaded Functionalized Solid Lipid Nanoparticles Intended for HIV Prevention
Formulation of Tenofovir-Loaded Functionalized Solid Lipid Nanoparticles Intended for HIV Prevention
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DOI：
10.1002/jps.22529
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发表时间：
2011-08-01
影响因子：
3.8
通讯作者：
Youan, Bi-Botti C.
中科院分区：
文献类型：
--
作者：
Alukda, Dima;Sturgis, Timothy;Youan, Bi-Botti C.
这项研究的目的是设计聚赖氨酸-肝素功能化固体脂质纳米粒(FSLN)，用于使用阴道杀菌剂递送模板来预防HIV。FSLN是用改进的倒相技术和随后的逐层沉积方法制备的。采用Box-Behnken实验设计，分析了三个因素(X-1=牛血清白蛋白浓度、X-2=水相的pH值、X-3=脂类的量)对动态光散射(DLS)所测颗粒平均直径(PMD)的影响。替诺福韦是一种新型的抗HIV微生物剂。通过电子显微镜、差示扫描量热法、紫外可见光谱和荧光光谱分析，分别对SLN的形态、Zeta电位(Zeta)、药物包封率(EE%)和对人阴道上皮细胞系的细胞毒性进行了表征。统计模型以90%的置信度预测颗粒大小(Y)，Y值受X-1和X-2的显著影响。制备的fSLN无细胞毒性，呈血小板状，PMD、EE%和Zeta值分别为153 nm、8.3%和-51 mV。这些局部给药的fSLN有可能增强细胞对疏水性杀菌剂的吸收，并在艾滋病毒/艾滋病感染过程中远离病毒，可能导致更有效地预防疾病传播。(C)2011年Wiley-Liss，Inc.和美国药剂师协会《医药科学》100：3345-3356,2011年
The objective of this study is to engineer polylysine-heparin functionalized solid lipid nanoparticles (fSLNs) for the use of a vaginal microbicide delivery template for HIV prevention. The fSLNs are prepared using a modified phase-inversion technique followed by a layer-by-layer deposition method. The Box-Behnken experimental design is used to analyze the influence of three factors (X-1 = bovine serum albumin concentration, X-2 = pH of the aqueous phase, and X-3 = lipid amount) on the particle mean diameter (PMD) measured by dynamic light scattering (DLS). Tenofovir is used as a model anti-HIV microbicide. The SLNs are also characterized for morphology, zeta potential (zeta), percent drug encapsulation efficiency (EE%), and cytotoxicity on a human vaginal epithelial cell line by electron microscopy, DLS, ultraviolet, and fluorescence spectroscopy, respectively. The statistical model predicts particle size (Y) with 90% confidence and the Y values are significantly affected by X-1 and X-2. The produced fSLNs appear noncytotoxic and exhibit a platelet-like shape with respective PMD, EE%, and zeta value of 153 nm, 8.3%, and - 51mV. These fSLNs intended to be administered topically have the potential to enhance cellular uptake of hydrophobic microbicides and outdistance the virus during the HIV/AIDS infection process, possibly leading to more effective prevention of the disease transmission. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100: 3345-3356, 2011