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羧甲基壳聚糖修饰的脂质纳米制剂作为一种高效且生物相容的口服抗利什曼原虫药物载体系统。

Carboxymethyl chitosan modified lipid nanoformulations as a highly efficacious and biocompatible oral anti-leishmanial drug carrier system.

作者信息

Singh Aakriti, Yadagiri Ganesh, Negi Manorma, Kushwaha Anurag Kumar, Singh Om Prakash, Sundar Shyam, Mudavath Shyam Lal

机构信息

Infectious Disease Biology Laboratory, Chemical Biology Unit, Institute of Nano Science and Technology, Knowledge City, Sector-81, Mohali, Punjab 140306, India.

Infectious Disease Research Laboratory, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India.

出版信息

Int J Biol Macromol. 2022 Apr 15;204:373-385. doi: 10.1016/j.ijbiomac.2022.02.006. Epub 2022 Feb 8.

Abstract

Herein, carboxymethyl chitosan (CMC) grafted lipid nanoformulations were facilely prepared by thin-film hydration method as a highly efficient biocompatible anti-leishmanial carrier encapsulating amphotericin B (AmB). Nanoformulations were characterized for their physicochemical characteristics wherein TEM analysis confirmed the spherical structure, whereas FTIR analysis revealed the conjugation of CMC onto nanoformulations and confirmed the free state of AmB. Furthermore, the wettability study confirmed the presence of CMC on the surface of nanoformulations attributed to the enhanced hydrophilicity. Surface hydrophilicity additionally contributes towards consistent mucin retention ability for up to 6 h, superior mucoadhesiveness, and hence enhanced bioavailability. The proposed nanoformulations with high encapsulation and drug loading properties displayed controlled drug release in the physiological microenvironment. In vitro, antileishmanial results showed an astounding 97% inhibition in amastigote growth. Additionally, in vivo studies showed that treatment with nanoformulations significantly reduced the liver parasitic burden (93.5%) without causing any toxicity when given orally.

摘要

在此,通过薄膜水化法简便地制备了羧甲基壳聚糖(CMC)接枝脂质纳米制剂,作为包封两性霉素B(AmB)的高效生物相容性抗利什曼原虫载体。对纳米制剂的物理化学特性进行了表征,其中透射电子显微镜(TEM)分析证实了其球形结构,而傅里叶变换红外光谱(FTIR)分析揭示了CMC与纳米制剂的缀合,并证实了AmB的游离状态。此外,润湿性研究证实了纳米制剂表面存在CMC,这归因于亲水性的增强。表面亲水性还有助于在长达6小时内保持一致的粘蛋白保留能力、卓越的粘膜粘附性,从而提高生物利用度。所提出的具有高包封率和载药性能的纳米制剂在生理微环境中显示出可控的药物释放。体外抗利什曼原虫结果显示,无鞭毛体生长的抑制率高达97%,令人震惊。此外,体内研究表明,口服纳米制剂治疗可显著降低肝脏寄生虫负荷(93.5%),且不会引起任何毒性。

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