Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan.
Department of Pharmacy, Iqra University, H-9 Campus, Islamabad 44000, Pakistan.
Int J Biol Macromol. 2023 Feb 1;227:1293-1304. doi: 10.1016/j.ijbiomac.2022.11.326. Epub 2022 Dec 5.
Topical treatment of cutaneous leishmaniasis holds great promise for decreasing drug associated side effects and improving efficacy. This study was aimed to develop mannosylated thiolated chitosan-coated silver nanoparticles (MTCAg) loaded emulgel for the treatment of cutaneous leishmaniasis. MTC-Ag were synthesized via a chemical reduction method and were loaded into the emulgel. The nanoparticles had a zeta potential of +19.8 mV, an average particle size of 115 nm and a narrow polydispersity index of 0.26. In-vitro release profiles showed controlled release of silver ions from both the MTC-Ag and the emulgel-loaded MTC-Ag nanoparticles after 24 h. An ex-vivo retention study indicated 5 times higher retention of silver by the emulgel-loaded MTC-Ag than by the MTC-Ag nanoparticles. The in-vitro anti-leishmanial assay revealed that MTC-Ag had an excellent inhibitory effect on intracellular amastigotes, leading to ~90 % inhibition at the highest concentration tested. A 4-fold reduction in the IC value was found for MTC-Ag compared to blank Ag nanoparticles. Cytotoxicity assay showed 83 % viability of macrophages for MTC-Ag and 30 % for Ag nanoparticles at a concentration of 80 μg/mL, demonstrating the improved biocompatibility of the polymeric nanoparticles. Drug release and retention studies corroborate the great potential of MTC-Ag-loaded emulgel for the treatment of cutaneous leishmaniasis.
局部治疗皮肤利什曼病有望减少与药物相关的副作用并提高疗效。本研究旨在开发甘露糖硫醇化壳聚糖包裹的载银纳米粒子(MTCAg)负载乳凝胶用于治疗皮肤利什曼病。MTC-Ag 通过化学还原法合成,并负载到乳凝胶中。纳米粒子的zeta 电位为+19.8 mV,平均粒径为 115nm,且具有较窄的多分散指数为 0.26。体外释放曲线显示,在 24 小时后,MTC-Ag 和负载于乳凝胶中的 MTC-Ag 纳米粒子均能控制银离子的释放。离体保留研究表明,负载于乳凝胶中的 MTC-Ag 比 MTC-Ag 纳米粒子保留 5 倍以上的银。体外抗利什曼原虫试验表明,MTC-Ag 对细胞内无鞭毛体具有极好的抑制作用,在最高测试浓度下抑制率约为 90%。与空白银纳米粒子相比,MTC-Ag 的 IC 值降低了 4 倍。细胞毒性试验表明,MTC-Ag 的巨噬细胞存活率为 83%,而银纳米粒子为 30%,在 80μg/mL 的浓度下,证明了聚合物纳米粒子具有更好的生物相容性。药物释放和保留研究证实了负载 MTC-Ag 的乳凝胶在治疗皮肤利什曼病方面具有巨大潜力。