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.
Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, University of Barcelona, Av. Joan XXIII, 27-31, Barcelona 08028, Spain.
Eur J Pharm Biopharm. 2017 Nov;120:98-106. doi: 10.1016/j.ejpb.2017.08.008. Epub 2017 Aug 24.
Despite the great effort to decrease the HIV infectivity rate, current antiretroviral therapy has several weaknesses; poor bioavailability, development of drug resistance and poor ability to access tissues. However, molecules such as peptides have emerged asa new expectative to HIV eradication. The vaginal mucosa is the main spreading point of HIV. There are natural barriers such as the vaginal fluid which protects the vaginal epithelium from any foreign agents reaching it. This work has developed and characterized Nanoparticles (NPs) coated with glycol chitosan (GC), loaded with an HIV-1 inhibitor peptide (E2). In vitro release and ex vivo studies were carried out using the vaginal mucosa of swine and the peptide was determined by HPLC MS/MS validated method. Moreover, the peptide was labeled with 5(6)-carboxyfluoresceine and entrapped into the NPs to carried out in vivo studies and to evaluate the NPs penetration and toxicity in the vaginal mucosa of the swine. The mean size of the NPs, ξ and the loading percentage were fundamental features for to reach the vaginal tissue and to release the peptide within intercellular space. The obtained results suggesting that the fusion inhibitor peptides loaded into the NPs coated with GC might be a new way to fight the HIV-1, due to the formulation might reach the human epithelial mucosa and release peptide without any side effects.
尽管已经付出了巨大的努力来降低 HIV 的感染率，但目前的抗逆转录病毒疗法仍存在一些弱点，如生物利用度差、耐药性的产生以及进入组织的能力差。然而，肽等分子已经成为 HIV 根除的新希望。阴道黏膜是 HIV 传播的主要部位。阴道内有阴道液等天然屏障，可以保护阴道上皮免受任何外来物质的侵害。本工作开发并表征了涂有乙二醇壳聚糖 (GC) 的纳米颗粒 (NPs)，并负载了一种 HIV-1 抑制剂肽 (E2)。采用猪阴道黏膜进行了体外释放和离体研究，并通过经 HPLC-MS/MS 验证的方法测定了肽。此外，还将肽用 5(6)-羧基荧光素进行标记并包封到 NPs 中，以进行体内研究并评估 NPs 在猪阴道黏膜中的穿透性和毒性。NPs 的平均粒径 ξ 和载药百分率是达到阴道组织并在细胞间隙释放肽的基本特征。研究结果表明，负载在 GC 涂层 NPs 中的融合抑制剂肽可能是对抗 HIV-1 的一种新方法，因为该制剂可能到达人上皮黏膜并释放肽，而不会产生任何副作用。
