Laboratório de Fitotecnologia, Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, Brazil.
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, Brazil.
Colloids Surf B Biointerfaces. 2019 Mar 1;175:306-313. doi: 10.1016/j.colsurfb.2018.12.003. Epub 2018 Dec 4.
Tuberculosis is an infectious bacterial disease that causes millions of deaths worldwide. Current treatment recommended by WHO is effective, however it is an extensive and arduous process associated to severe adverse effects, which induces a low patient compliance and the emerging of multidrug resistant tuberculosis. Thus, as a main goal of this study, rifampicin nanoparticles were surface functionalized with a tuftsin-modifed peptide to selectively recognize receptors located on infected alveolar macrophages, enhancing nanoparticles uptake by these cells and improving antimycobacterial activity. A tuftsin-based modified peptide was synthesized and successfully attached to nanoparticles interface (NP-pRIF). In parallel, nanoparticles without peptide were also developed for comparison (NP-RIF). Physicochemical characterization demonstrated that stable and monodisperse nanodelivery systems were obtained, with a controlled drug release profile and non-cytotoxic potential. Moreover, nanoparticles containing peptide were significantly more internalized by macrophages than nanoparticles without peptide over a wide range of time. Both nanoparticles were 2-fold more effective against M. tuberculosis than free rifampicin, suggesting NP-pRIF as a promising strategy for the management of tuberculosis treatment.
肺结核是一种传染性细菌性疾病，在全球范围内导致数百万人死亡。世界卫生组织目前推荐的治疗方法是有效的，然而，它是一个广泛而艰巨的过程，伴随着严重的不良反应，导致患者的依从性低，出现耐多药肺结核。因此，作为这项研究的主要目标，利福平纳米颗粒的表面功能化用了一个 tuftsin 修饰的肽，以选择性地识别位于受感染的肺泡巨噬细胞上的受体，增强这些细胞对纳米颗粒的摄取，并提高抗分枝杆菌活性。合成了一种基于 tuftsin 的修饰肽，并成功地连接到纳米颗粒的界面上（NP-pRIF）。同时，也开发了没有肽的纳米颗粒作为对照（NP-RIF）。物理化学特性表明，得到了稳定的单分散纳米递药系统，具有可控的药物释放曲线和非细胞毒性潜力。此外，含有肽的纳米颗粒在广泛的时间范围内比没有肽的纳米颗粒更能被巨噬细胞内化。两种纳米颗粒对结核分枝杆菌的作用均比游离利福平强 2 倍，表明 NP-pRIF 是治疗肺结核的一种很有前途的策略。
