The purpose of this study was to engineer a model anti-HIV microbicide (tenofovir) drug delivery system targeting HIV-1 envelope glycoprotein gp120 (HIV-1 g120) for the prevention of HIV sexual transmission. HIV-1 g120 and mannose responsive particles (MRP) were prepared through the layer-by-layer coating of calcium carbonate (CaCO₃) with concanavalin A (Con A) and glycogen. MRP average particle size ranged from 881.7 ± 15.45 nm to 1130 ± 15.72 nm, depending on the number of Con A layers. Tenofovir encapsulation efficiency in CaCO₃ was 74.4% with drug loading of 16.3% (w/w). MRP was non-cytotoxic to Lactobacillus crispatus, human vaginal keratinocytes (VK2), and murine macrophage RAW 264.7 cells and did not induce any significant proinflammatory nitric oxide release. Overall, compared to control, no statistically significant increase in proinflammatory cytokine IL-1α, IL-1β, IL-6, MKC, IL-7, and interferon-γ-inducible protein 10 (IP10) levels was observed. Drug release profiles in the presence of methyl α-d-mannopyranoside and recombinant HIV-1 envelope glycoprotein gp120 followed Hixson–Crowell and Hopfenberg kinetic models, indicative of a surface-eroding system. The one Con A layer containing system was found to be the most sensitive (∼2-fold increase in drug release vs control SFS:VFS) at the lowest HIV gp120 concentration tested (25 μg/mL). Percent mucoadhesion, tested ex vivo on porcine vaginal tissue, ranged from 10% to 21%, depending on the number of Con A layers in the formulation. Collectively, these data suggested that the proposed HIV-1 g120 targeting, using MRP, potentially represent a safe and effective template for vaginal microbicide drug delivery, if future preclinical studies are conclusive.

中文翻译：

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针对HIV-1 gp120的逐层工程杀微生物剂药物递送系统：物理化学和生物学特性

这项研究的目的是设计一种针对HIV-1包膜糖蛋白gp120（HIV-1 g120）的抗HIV杀微生物剂（替诺福韦）药物递送系统模型，以预防HIV性传播。通过用伴刀豆球蛋白A（Con A）和糖原的碳酸钙（CaCO ₃）的逐层包衣制备HIV-1 g120和甘露糖反应性颗粒（MRP）。MRP的平均粒径范围为881.7±15.45 nm至1130±15.72 nm，具体取决于Con A层的数量。替诺福韦在CaCO _3中的包封率为74.4％，载药量为16.3％（w / w）。MRP对曲霉乳杆菌无细胞毒性，人类阴道角质形成细胞（VK2）和鼠巨噬细胞RAW 264.7细胞，并且不会诱导任何明显的促炎性一氧化氮释放。总体而言，与对照组相比，未观察到促炎细胞因子IL-1α，IL-1β，IL-6，MKC，IL-7和干扰素-γ诱导型蛋白10（IP10）水平的统计学显着增加。在存在甲基α- d-甘露吡喃糖苷和重组HIV-1包膜糖蛋白gp120的情况下，药物释放曲线遵循Hixson-Crowell和Hopfenberg动力学模型，表明存在表面侵蚀系统。发现在最低的HIV gp120浓度（25μg/ mL）下，含有一个Con A层的系统最敏感（药物释放量是对照SFS：VFS的2倍）。粘膜粘连百分比，离体测试取决于制剂中Con A层的数量，在猪阴道组织中的含量在10％到21％之间。总体而言，这些数据表明，如果未来的临床前研究具有决定性意义，则使用MRP拟议的HIV-1 g120靶向靶向可能代表阴道杀菌剂药物输送的安全有效模板。