a UCIBIO, REQUIMTE, Departamento de Ciências Químicas , Faculdade de Farmácia, Universidade do Porto , Porto , Portugal.
b UCIBIO, REQUIMTE, Laboratório de Tecnologia Farmacêutica, Departamento de Ciências do Medicamento , Faculdade de Farmácia, Universidade do Porto , Porto , Portugal.
Artif Cells Nanomed Biotechnol. 2018;46(sup1):653-663. doi: 10.1080/21691401.2018.1434186. Epub 2018 Feb 12.
Tuberculosis (TB) is still a devastating disease and more people have died of TB than any other infectious diseases throughout the history. The current therapy consists of a multidrug combination in a long-term treatment, being associated with the appearance of several adverse effects. Thus, solid lipid nanoparticles (SLNs) were developed using mannose as a lectin receptor ligand conjugate for macrophage targeting and to increase the therapeutic index of rifampicin (RIF). The developed SLNs were studied in terms of diameter, polydispersity index, zeta potential, encapsulation efficiency (EE) and loading capacity (LC). Morphology, in vitro drug release and differential scanning calorimetry studies, macrophage uptake studies, cell viability and storage stability studies were also performed. The diameter of the SLNs obtained was within the range of 160-250 nm and drug EE was above 75%. The biocompatibility of M-SLNs was verified and the internalization in macrophages was improved with the mannosylation. The overall results suggested that the developed mannosylated formulations are safe and a promising tool for TB therapy targeted for macrophages.
结核病（TB）仍然是一种毁灭性疾病，在整个历史上，死于结核病的人数比死于任何其他传染病的人数都多。目前的治疗方法包括长期使用多种药物联合治疗，这与出现多种不良反应有关。因此，开发了固体脂质纳米粒（SLNs），并使用甘露糖作为凝集素受体配体缀合物进行巨噬细胞靶向，以提高利福平（RIF）的治疗指数。对所开发的 SLNs 进行了粒径、多分散指数、Zeta 电位、包封效率（EE）和载药量（LC）的研究。还进行了形态学、体外药物释放和差示扫描量热法研究、巨噬细胞摄取研究、细胞活力和储存稳定性研究。所得到的 SLNs 的粒径在 160-250nm 范围内，药物 EE 超过 75%。验证了 M-SLNs 的生物相容性，甘露糖基化可提高其在巨噬细胞中的内化作用。总的来说，研究结果表明，所开发的甘露糖基化制剂是安全的，是一种有前途的针对巨噬细胞的结核病治疗工具。
