Laboratório de Tecnologia Farmacêutica, Programa de Pós-graduação em Ciências Farmacêuticas, Centro de Ciências da Saúde, Departamento de Farmácia Industrial, Universidade Federal de Santa Maria, Santa Maria, 97105-900, Brazil.
Departamento de Ciências Básicas da Saúde, Programa de Pós-graduação em Biociências, Universidade Federal de Ciências da Saúde, Porto Alegre, Brazil.
AAPS PharmSciTech. 2019 Jan 7;20(2):49. doi: 10.1208/s12249-018-1240-8.
3,3'-Diindolylmethane (DIM) is a phytochemical that presents health benefits (antitumor, antioxidant, and anti-inflammatory effects). However, it is water insoluble and thermo- and photolabile, restraining its pharmaceutical applications. As a strategy to overcome such limitations, this study aimed the development and characterization of DIM-loaded nanocapsules (NCs) prepared with different compositions as well as the in vitro assessment of scavenging activity and cytotoxicity. The formulations were obtained using the interfacial deposition of preformed polymer method and were composed by Eudragit® RS100 or ethylcellulose as polymeric wall and primula or apricot oil as the core. All the formulations had adequate physicochemical characteristics: nanometric size (around 190 nm), low polydispersity index (< 0.2), pH value at acid range, high values of zeta potential, drug content, and encapsulation efficiency (~ 100%). Besides, nanoencapsulation protected DIM against UVC-induced degradation and increased the scavenging activity assessed by the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) and 1-1-diphenyl-2-picrylhydrazyl methods. The developed DIM-loaded nanocapsules were further evaluated regarding the in vitro release profile and cytotoxicity against a human glioblastoma cell line (U87 cells). The results demonstrated that the nanoencapsulation promoted a sustained release of the bioactive compound (in the range of 58-78% after 84 h) in comparison to its free form (86% after 12 h), as well as provided a superior cytotoxic effect against the U87 cells in the highest concentrations. Therefore, our results suggest that nanoencapsulation could be a promising approach to overcome the DIM physicochemical limitations and potentialize its biological properties.
3,3'-二吲哚甲烷（DIM）是一种具有健康益处（抗肿瘤、抗氧化和抗炎作用）的植物化学物质。然而，它不溶于水，且对热和光不稳定，这限制了其在药物方面的应用。作为克服这些限制的一种策略，本研究旨在开发和表征用不同组成制备的负载 DIM 的纳米胶囊（NC），并对其清除活性和细胞毒性进行体外评估。这些配方是通过界面沉积法制备的，由 Eudragit® RS100 或乙基纤维素作为聚合物壁，报春花油或杏仁油作为核。所有配方均具有良好的物理化学特性：纳米级尺寸（约 190nm）、低多分散指数（<0.2）、酸性 pH 值、高 Zeta 电位、药物含量和包封效率（约 100%）。此外，纳米封装保护 DIM 免受 UVC 诱导的降解，并提高了通过 2,2'-联氮双（3-乙基苯并噻唑啉-6-磺酸）和 1-1-二苯基-2-苦基肼评估的清除活性。进一步评估了所开发的负载 DIM 的纳米胶囊的体外释放特性和对人神经胶质瘤细胞系（U87 细胞）的细胞毒性。结果表明，与游离形式相比（12 小时后 86%），纳米封装促进了生物活性化合物的持续释放（84 小时后释放范围为 58-78%），并且在最高浓度下对 U87 细胞具有更好的细胞毒性作用。因此，我们的结果表明，纳米封装可能是克服 DIM 理化限制并增强其生物学特性的一种有前途的方法。
