PDF(Pubmed)
Abstract：
Chagas disease (CD) is a worldwide public health problem. Benznidazole (BZ) is the drug used to treat it. However, in its commercial formulation, it has significant side effects and is less effective in the chronic phase of the infection. The development of particulate systems containing BZ is therefore being promoted. The objective of this investigation was to develop polymeric nanoparticles loaded with BZ and examine their trypanocidal impact in vitro. Two formulas (BNP1 and BNP2) were produced through double emulsification and freeze drying. Subsequent to physicochemical and morphological assessment, both formulations exhibited adequate yield, average particle diameter, and zeta potential for oral administration. Cell viability was assessed in H9C2 and RAW 264.7 cells in vitro, revealing no cytotoxicity in cardiomyocytes or detrimental effects in macrophages at specific concentrations. BNP1 and BNP2 enhanced the effect of BZ within 48 h using a treatment of 3.90 μg/mL. The formulations notably improved NO reduction, particularly BNP2. The findings imply that the compositions are suitable for preclinical research, underscoring their potential as substitutes for treating CD. This study aids the quest for new BZ formulations, which are essential in light of the disregard for the treatment of CD and the unfavorable effects associated with its commercial product.
摘要：
南美锥虫病（CD）是一个世界性的公共卫生问题。苯并硝唑（BZ）是用于治疗它的药物。然而,在其商业配方中，它有明显的副作用，在感染的慢性期效果较差。因此促进了含有BZ的颗粒系统的开发。本研究的目的是开发负载有BZ的聚合物纳米颗粒并在体外检查它们的杀锥虫作用。通过双乳化和冷冻干燥制备两种配方(BNP1和BNP2)。在物理化学和形态学评估之后，两种配方都表现出足够的产量，平均粒径,和口服给药的ζ电位。在体外H9C2和RAW264.7细胞中评估细胞活力，在特定浓度下，在心肌细胞中没有细胞毒性或在巨噬细胞中没有有害作用。BNP1和BNP2使用3.90μg/mL的处理在48小时内增强了BZ的作用。配方显著改善了NO的减少，特别是BNP2。这些发现暗示这些组合物适用于临床前研究，强调他们作为治疗CD的替代品的潜力。这项研究有助于寻找新的BZ配方，鉴于无视CD的治疗以及与其商业产品相关的不利影响，这是必不可少的。
