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无有机溶剂苯硝唑纳米混悬液作为一种新型儿科锥虫病制剂的方法。

Organic solvent-free benznidazole nanosuspension as an approach to a novel pediatric formulation for Chagas disease.

机构信息

Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba (UNC), 1-4 Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba, X5000HUA, Argentina.

Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET/UNC, 1-4 Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba, X5000HUA, Argentina.

出版信息

Ther Deliv. 2024;15(9):699-716. doi: 10.1080/20415990.2024.2380244. Epub 2024 Aug 5.

Abstract

Benznidazole (BNZ), a class-II drug, is the primary treatment for Chagas disease, but its low aqueous solubility presents challenges in formulation and efficacy. Nanosuspensions (NS) could potentially address these issues. BNZ-NS were prepared using a simple, organic solvents-free nano-milling approach. Physicochemical characterizations were conducted on both NS and lyophilized solid-state BNZ-nanocrystals (NC). BNZ-NS exhibited particle size <500 nm, an acceptable polydispersity index (0.23), high Z-potential, and physical stability for at least 90 days. BNZ-NC showed tenfold higher solubility than pure BNZ. Dissolution assays revealed rapid BNZ-NS dissolution. BNZ-NC demonstrated biocompatibility on an eukaryotic cell and enhanced BNZ efficacy against trypomastigotes of . BNZ-NS offers a promising alternative, overcoming limitations associated with BNZ for optimized pharmacotherapy.

摘要

苯硝唑(BNZ)是一种 II 类药物,是恰加斯病的主要治疗药物,但它的水溶解度低,在制剂和疗效方面存在挑战。纳米混悬剂(NS)可能解决这些问题。BNZ-NS 是使用简单的、无有机溶剂的纳米研磨方法制备的。对 NS 和冻干固态 BNZ-纳米晶体(NC)进行了物理化学特性分析。BNZ-NS 的粒径<500nm,可接受的多分散指数(0.23),高 Z 电位,至少 90 天的物理稳定性。BNZ-NC 的溶解度比纯 BNZ 高 10 倍。溶解试验表明 BNZ-NS 迅速溶解。BNZ-NC 在真核细胞上表现出生物相容性,并增强了 BNZ 对 滋养体的疗效。BNZ-NS 提供了一种有前途的替代方法,克服了 BNZ 优化药物治疗的相关限制。

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