Department of Biosciences, University of Oslo, Blindernveien 31, 0371 Oslo, Norway.
Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, C/Mariano Esquillor s/n, 50018 Zaragoza, Spain.
Biomater Sci. 2023 Mar 14;11(6):2103-2114. doi: 10.1039/d2bm01835g.
The combination drug regimens that have long been used to treat tuberculosis (TB), caused by , are fraught with problems such as frequent administration, long duration of treatment, and harsh adverse effects, leading to the emergence of multidrug resistance. Moreover, there is no effective preventive vaccine against TB infection. In this context, nanoparticles (NPs) have emerged as a potential alternative method for drug delivery. Encapsulating antibiotics in biodegradable NPs has been shown to provide effective therapy and reduced toxicity against in different mammalian models, when compared to conventional free drug administration. Here, we evaluate the localization, therapeutic efficacy and toxic effects of polymeric micellar NPs encapsulating a promising but highly hydrophobic and toxic antitubercular drug bedaquiline (BQ) in zebrafish embryos infected with Our study shows that the NP formulation of BQ improves survival and reduces bacterial burden in the infected embryos after treatment when compared to its free form. The intravenously injected BQ NPs have short circulation times due to their rapid and efficient uptake into the endothelial cells, as observed by correlative light and electron microscopy (CLEM).
长期以来，联合药物疗法一直被用于治疗结核分枝杆菌（ ）引起的结核病，但存在频繁给药、治疗时间长和严重不良反应等问题，导致出现了耐多药结核分枝杆菌。此外，目前还没有针对结核分枝杆菌感染的有效预防疫苗。在这种情况下，纳米颗粒（NPs）已成为一种有潜力的药物递送替代方法。与传统的游离药物给药相比，将抗生素封装在可生物降解的 NPs 中已被证明可在不同的哺乳动物模型中提供针对结核分枝杆菌的有效治疗并降低毒性。在这里，我们评估了在感染结核分枝杆菌的斑马鱼胚胎中，包封有前途但高度疏水和有毒的抗结核药物贝达喹啉（BQ）的聚合物胶束 NPs 的定位、治疗效果和毒性作用。我们的研究表明，与游离形式相比，BQ 的 NP 制剂在治疗后可提高感染胚胎的存活率并降低细菌负荷。静脉注射的 BQ NPs 由于其迅速而有效地被内皮细胞摄取，因此在相关的光镜和电子显微镜（CLEM）下观察到其循环时间很短。
