Departamento de Farmacia Galénica y Tecnología Alimentaria, Facultad de Farmacia, Pl. Ramón y Cajal s/n, Universidad Complutense de Madrid, 28040, Madrid, Spain.
Facultad de Farmacia, Pl. Ramón y Cajal s/n, Instituto Universitario de Farmacia Industrial, Universidad Complutense de Madrid, 28040, Madrid, Spain.
AAPS PharmSciTech. 2019 Dec 5;21(1):15. doi: 10.1208/s12249-019-1552-3.
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis and represents one of the leading causes of mortality worldwide due to multidrug-resistant TB (MDR-TB). In our work, a new formulation of biodegradable PLGA microparticles was developed for pulmonary administration of gatifloxacin, using a surface modifier agent to actively target alveolar macrophages thereby allowing to gain access of the drug to Mycobacterium tuberculosis. For this, rapid uptake of the particles by macrophages is beneficial. This process was evaluated with fluorescein-loaded microparticles using PLGA 502 or PLGA 502H as polymers and labrafil as surface modifier. Cell phagocytosis was studied in raw 264.7 mouse macrophage cell line after 3, 5, 24, and 48 h incubation with the microparticles. Labrafil enhanced the uptake rate of PLGA 502H microparticles by macrophages which was directly related to the modification of the polymer matrix. Gatifloxacin-loaded PLGA microparticles using PLGA 502 or PLGA 502H and labrafil were prepared. From our results, only microparticles prepared with PLGA 502H and labrafil exhibited high encapsulation efficiency (89.6 ± 0.2%), rapid phagocytosis by macrophages (3 h), and remained inside the cells for at least 48 h, thereby resulting in a suitable carrier to potentially treat MDR-TB.
结核病（TB）是由结核分枝杆菌引起的传染病，是全球因耐多药结核病（MDR-TB）导致死亡的主要原因之一。在我们的工作中，开发了一种新的可生物降解 PLGA 微球制剂，用于肺部给予加替沙星，使用表面修饰剂主动靶向肺泡巨噬细胞，从而使药物能够进入结核分枝杆菌。为此，药物被巨噬细胞快速摄取是有益的。使用 PLGA 502 或 PLGA 502H 作为聚合物和 Labrafil 作为表面修饰剂，用荧光素负载的微球来评估这一过程。在用微球孵育 RAW 264.7 小鼠巨噬细胞系 3、5、24 和 48 小时后，研究了细胞吞噬作用。Labrafil 增强了巨噬细胞对 PLGA 502H 微球的摄取率，这与聚合物基质的修饰直接相关。使用 PLGA 502 或 PLGA 502H 和 Labrafil 制备了载加替沙星的 PLGA 微球。从我们的结果来看，只有用 PLGA 502H 和 Labrafil 制备的微球表现出高包封效率（89.6±0.2%）、被巨噬细胞快速吞噬（3 小时），并至少在细胞内保留 48 小时，因此是一种有潜力治疗耐多药结核病的合适载体。
