Britta Elizandra Aparecida, da Silva Cleuza Conceição, Rubira Adley Forti, Nakamura Celso Vataru, Borsali Redouane
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Brazil.
Departamento de Química, Universidade Estadual de Maringá, Brazil.
Mater Sci Eng C Mater Biol Appl. 2016 Dec 1;69:1159-66. doi: 10.1016/j.msec.2016.08.021. Epub 2016 Aug 8.
Thiosemicarbazones are an important class of compounds that have been extensively studied in recent years, mainly because of their broad profile of pharmacological activity. A new 4-nitrobenzaldehyde thiosemicarbazone compound (BZTS) that was derived from S-limonene has been demonstrated to have significant antiprotozoan activity. However, the hydrophobic characteristic of BZTS limits its administration and results in low oral bioavailability. In the present study, we proposed the synthesis of nanoparticle-based block copolymers that can encapsulate BZTS, with morphological evaluation of the nanoparticle suspensions being performed by transmission and cryo-transmission electronic microscopy. The mean particle sizes of the nanoparticle suspensions were determined by static light and dynamic light scattering (SLS/DLS), and the hydrodynamic radius (Rh) was determined using the Stokes-Einstein equation. The zeta potential (ζ) and polydispersity index (PDI) were also determined. The entrapment encapsulation efficiency of the BZTS nanoparticles was measured by ultraviolet spectrophotometry. In vitro activity of BZTS nanoparticle suspensions against intracellular amastigotes of Leishmania amazonensis and cytotoxic activity were also evaluated. The results showed the production of spherical nanoparticles with varied sizes depending on the hydrophobic portion of the amphiphilic diblock copolymers used. Significant concentration-dependent inhibitory activity against intracellular amastigotes was observed, and low cytotoxic activity was demonstrated against macrophages.
硫代氨基脲是近年来得到广泛研究的一类重要化合物，主要是因为它们具有广泛的药理活性。一种从S-柠檬烯衍生而来的新型4-硝基苯甲醛硫代氨基脲化合物（BZTS）已被证明具有显著的抗原生动物活性。然而，BZTS的疏水特性限制了其给药方式，并导致口服生物利用度较低。在本研究中，我们提出合成可包裹BZTS的基于纳米颗粒的嵌段共聚物，并通过透射电子显微镜和冷冻透射电子显微镜对纳米颗粒悬浮液进行形态学评估。通过静态光散射和动态光散射（SLS/DLS）测定纳米颗粒悬浮液的平均粒径，并使用斯托克斯-爱因斯坦方程确定流体力学半径（Rh）。还测定了zeta电位（ζ）和多分散指数（PDI）。通过紫外分光光度法测定BZTS纳米颗粒的包封率。还评估了BZTS纳米颗粒悬浮液对亚马逊利什曼原虫细胞内无鞭毛体的体外活性和细胞毒性活性。结果表明，根据所用两亲性二嵌段共聚物的疏水部分，可产生大小各异的球形纳米颗粒。观察到对细胞内无鞭毛体有显著的浓度依赖性抑制活性，并且对巨噬细胞显示出低细胞毒性活性。
