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载银纳米粒的甘露糖硫醇化壳聚糖前体胶用于治疗皮肤利什曼病。

Emulgel-loaded mannosylated thiolated chitosan-coated silver nanoparticles for the treatment of cutaneous leishmaniasis.

机构信息

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.

出版信息

Int J Biol Macromol. 2023 Feb 1;227:1293-1304. doi: 10.1016/j.ijbiomac.2022.11.326. Epub 2022 Dec 5.

Abstract

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.

摘要

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。

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