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用于血吸虫病干预的抗体功能化脂质纳米系统的体内评价

In Vivo Evaluation of an Antibody-Functionalized Lipoidal Nanosystem for Schistosomiasis Intervention.

作者信息

Adekiya Tayo A, Kumar Pradeep, Kondiah Pierre P D, Choonara Yahya E

机构信息

Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa.

出版信息

Pharmaceutics. 2022 Jul 22;14(8):1531. doi: 10.3390/pharmaceutics14081531.

Abstract

This study employed nanotechnological techniques to design and develop a praziquantel nanoliposomal (NLP) system and surface-functionalized the NLP with anti-calpain antibody (anti-calpain-NLP) for targeted praziquantel (PZQ) delivery in the treatment of schistosomiasis. Anti-calpain-NLPs were prepared and validated for their physicochemical parameters, in vitroand in vivotoxicity, drug entrapment efficiency (DEE), drug loading capacity (DLC), drug release, and parasitological cure rate. The particle sizes for the formulated nanoliposomes ranged from 88.3 to 92.7 nm (PDI = 0.17-0.35), and zeta potential ranged from -20.2 to -31.9 mV. The DLC and DEE ranged from 9.03 to 14.16 and 92.07 to 94.63, respectively. The functionalization of the nanoliposome surface was stable, uniform, and spherical. Fourier-transform infrared (FTIR), thermal behavior and X-ray powder diffraction (XRPD) analysis confirmed that the anti-calpain antibody and PZQ were attached to the surface and the nanoliposomes inner core, respectively. The drug sustained release was shown to be 93.2 and 91.1% within 24 h for NLP and anti-calpain-NLP, respectively. In thein vitroanalysis study, the nanoliposome concentrations range of 30 to 120 μg/mL employed revealed acceptable levels of cell viability, with no significant cytotoxic effects on RAW 264.7 murine macrophage as well as 3T3 human fibroblast cells. Biochemical markers and histopathological analysis showed that the formulated nanoliposomes present no or minimal oxidative stress and confer hepatoprotective effects on the animals. The findings so obtained supported the ability of oral anti-calpain-NLP to target young and adult schistosomes in the liver and porto-mesenteric locations, resulting in improved effectiveness of PZQ.

摘要

本研究采用纳米技术设计并开发了吡喹酮纳米脂质体(NLP)系统,并用抗钙蛋白酶抗体对NLP进行表面功能化(抗钙蛋白酶-NLP),以实现吡喹酮(PZQ)的靶向递送,用于治疗血吸虫病。制备了抗钙蛋白酶-NLP,并对其理化参数、体外和体内毒性、药物包封率(DEE)、载药量(DLC)、药物释放和寄生虫治愈率进行了验证。所制备的纳米脂质体粒径范围为88.3至92.7nm(PDI = 0.17 - 0.35),zeta电位范围为-20.2至-31.9mV。DLC和DEE分别为9.03至14.16和92.07至94.63。纳米脂质体表面功能化稳定、均匀且呈球形。傅里叶变换红外(FTIR)、热行为和X射线粉末衍射(XRPD)分析证实,抗钙蛋白酶抗体和PZQ分别附着在表面和纳米脂质体内核。NLP和抗钙蛋白酶-NLP的药物缓释率在24小时内分别为93.2%和91.1%。在体外分析研究中,所采用的纳米脂质体浓度范围为30至120μg/mL,显示出可接受的细胞活力水平,对RAW 264.7小鼠巨噬细胞以及3T3人成纤维细胞均无明显细胞毒性作用。生化标志物和组织病理学分析表明,所制备的纳米脂质体对动物无氧化应激或氧化应激极小,并具有肝脏保护作用。 这些结果支持口服抗钙蛋白酶-NLP能够靶向肝脏和门静脉肠系膜部位的幼年和成年血吸虫,从而提高PZQ的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c8e/9332388/a54da743a63e/pharmaceutics-14-01531-g001.jpg

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