Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan; Riphah Institute of Pharmaceutical Sciences (RIPS), Riphah International University, Lahore Campus, Lahore, Pakistan; Department of Pathology, Ohio State University Medical Center, Columbus, OH 43201, United States.
Department of Pathology, Ohio State University Medical Center, Columbus, OH 43201, United States.
Eur J Pharm Biopharm. 2020 Jul;152:307-317. doi: 10.1016/j.ejpb.2020.05.029. Epub 2020 May 30.
The present study aimed on the site specific delivery and enhanced in-vivo efficacy of antimonial drugs against the visceral leishmaniasis via macrophage targeted mannose anchored thiomer based nanoparticles. Mannose anchored thiolated nanoformulation [M-(CS-g-PEI)-TGA] was developed and evaluated in terms particle size, zeta-potential and entrapment efficacy. The TEM and EDX analysis was carried out to evaluate the morphology and successful entrapment of antimonial drug. Mucodhesion, permeation enhancement, oral pharmacokinetics, and in-vivo anti-leishmanial activity were carried out. The M-(CS-g-PEI)-TGA were found to be spherical having particle size of 287 ± 20 nm. Ex-vivo permeation indicated a 7.39-fold enhanced permeation of Meglumine Antimoniate with M-(CS-g-PEI)-TGA across Caco-2 cells compared to the Glucantime. Evaluation of in-vitro reduction in the parasitic burden via flow cytometric analysis indicated a 5.7-fold lower IC for M-(CS-g-PEI)-TGA compared to Glucantime. A 6.1-fold improvement in the oral bioavailability and 5.2-fold reduced parasitic burden in the L. donovani infected BALB/c mice model was observed with M-(CS-g-PEI)-TGA compared to Glucantime. The results encouraged the concept of M-(CS-g-PEI)-TGA nanoformulations as a promising strategy for oral therapy against visceral leishmaniasis.
本研究旨在通过巨噬细胞靶向甘露糖锚定硫醚键纳米颗粒实现锑剂在体内的靶向传递和增强疗效，以治疗内脏利什曼病。我们制备并评价了甘露糖锚定硫代纳米制剂[M-(CS-g-PEI)-TGA]的粒径、Zeta 电位和包封效率。通过 TEM 和 EDX 分析评价了纳米粒的形态和载药情况。进行了黏附性、渗透增强、口服药代动力学和体内抗利什曼原虫活性评价。结果显示，M-(CS-g-PEI)-TGA 为球形，粒径为 287±20nm。体外渗透实验表明，与 Glucantime 相比，M-(CS-g-PEI)-TGA 使麦格胺锑的渗透增加了 7.39 倍。通过流式细胞术分析评估体外寄生虫载量的减少，结果表明 M-(CS-g-PEI)-TGA 的 IC50 比 Glucantime 低 5.7 倍。与 Glucantime 相比，M-(CS-g-PEI)-TGA 在感染利什曼原虫的 BALB/c 小鼠模型中的口服生物利用度提高了 6.1 倍，寄生虫载量降低了 5.2 倍。这些结果鼓励了 M-(CS-g-PEI)-TGA 纳米制剂作为治疗内脏利什曼病口服疗法的一种有前途的策略。
