Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry , University of Barcelona , Av. Joan XXIII, 27-31 , Barcelona 08028 , Spain.
Unit of Synthesis and Biomedical Application of Peptides, Department of Biomedical Chemistry , IQAC-CSIC , Jordi Girona 18 , 08034 Barcelona , Spain.
Mol Pharm. 2018 Nov 5;15(11):5005-5018. doi: 10.1021/acs.molpharmaceut.8b00609. Epub 2018 Oct 3.
New therapeutic alternatives to fight against the spread of HIV-1 are based on peptides designed to inhibit the early steps of HIV-1 fusion in target cells. However, drawbacks, such as bioavailability, short half-life, rapid clearance, and poor ability to cross the physiological barriers, make such peptides unattractive for the pharmaceutical industry. Here we developed, optimized, and characterized polymeric nanoparticles (NPs) coated with glycol chitosan to incorporate and release an HIV-1 fusion inhibitor peptide (E1) inside the vaginal mucosa. The NPs were prepared by a modified double emulsion method, and optimization was carried out by a factorial design. In vitro, ex vivo, and in vivo studies were carried out to evaluate the optimized formulation. The results indicate that the physicochemical features of these NPs enable them to incorporate and release HIV fusion inhibitor peptides to the vaginal mucosa before the fusion step takes place.
新型治疗方法可用于对抗 HIV-1 的传播，其基于设计用于抑制 HIV-1 在靶细胞中融合的早期步骤的肽。然而，缺点，如生物利用度、半衰期短、快速清除和穿越生理屏障的能力差，使得这些肽对制药行业没有吸引力。在这里，我们开发、优化并表征了涂有乙二醇壳聚糖的聚合物纳米颗粒 (NPs)，以在阴道黏膜内包封和释放 HIV-1 融合抑制剂肽 (E1)。NPs 通过改良的双重乳液法制备，并通过析因设计进行优化。进行了体外、离体和体内研究来评估优化的配方。结果表明，这些 NPs 的物理化学特性使它们能够在融合步骤发生之前将 HIV 融合抑制剂肽包封并递送到阴道黏膜。
