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载抗 CCR5siRNA 聚己内酯纳米粒的制备及表征用于局部暴露前预防。

Production and Characterization of Anti-CCR5 siRNA-Loaded Polycaprolactone Nanoparticles for Topical Pre-exposure Prophylaxis.

机构信息

i3S-Instituto de Investigação e Inovação em Saúde & INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal.

CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Gandra, Portugal.

出版信息

Methods Mol Biol. 2021;2282:403-416. doi: 10.1007/978-1-0716-1298-9_22.

Abstract

Topical posttranscriptional silencing of host factors involved in HIV-1 sexual transmission, such as CCR5, presents the potential to prevent new cases of infection. However, issues concerning proper engineering of safe and effective delivery systems for anti-CCR5 siRNA may impair the ability to yield suitable silencing at the mucosal level. Here we describe the production protocol of anti-CCR5 siRNA-loaded polycaprolactone-based nanoparticles (≈100 nm). Furthermore, we present data regarding the physicochemical and in vitro biological characterization of obtained nanosystems, which support their potential as microbicide candidates for topical pre-exposure prophylaxis of HIV-1 infection.

摘要

靶向性抑制宿主细胞中与 HIV-1 性传播相关的因子(如 CCR5),可能会预防新的感染病例。但是,用于抗 CCR5siRNA 的安全有效的递药系统的适当工程化问题,可能会削弱在黏膜水平上产生有效沉默的能力。本研究描述了载有抗 CCR5siRNA 的基于聚己内酯的纳米颗粒(≈100nm)的生产方案。此外,我们还提供了有关所得纳米系统的理化和体外生物学特性的研究数据,这支持了它们作为用于 HIV-1 感染的局部暴露前预防的杀微生物剂候选物的潜力。

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