Zanotto-Filho Alfeu, Coradini Karine, Braganhol Elizandra, Schröder Rafael, de Oliveira Cláudia Melo, Simões-Pires André, Battastini Ana Maria Oliveira, Pohlmann Adriana Raffin, Guterres Sílvia Stanisçuaski, Forcelini Cassiano Mateus, Beck Ruy Carlos Ruver, Moreira José Cláudio Fonseca
Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil.
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
Eur J Pharm Biopharm. 2013 Feb;83(2):156-67. doi: 10.1016/j.ejpb.2012.10.019. Epub 2012 Nov 28.
In this study, we developed curcumin-loaded lipid-core nanocapsules (C-LNCs) in an attempt to improve the antiglioma activity of this polyphenol. C-LNC showed nanotechnological properties such as nanometric mean size (196 nm), 100% encapsulation efficiency, polydispersity index below 0.1, and negative zeta potential. The in vitro release assays demonstrated a controlled release of curcumin from lipid-core nanocapsules. In C6 and U251MG gliomas, C-LNC promoted a biphasic delivery of curcumin: the first peak occurred early in the treatment (1-3h), whereas the onset of the second phase occurred after 48 h. In C6 cells, the cytotoxicity of C-LNC was comparable to non-encapsulated curcumin only after 96 h, whereas C-LNCs were more cytotoxic than non-encapsulated curcumin after 24h of incubation in U251MG. Induction of G2/M arrest and autophagy were observed in C-LNC as well as in free-curcumin treatments. In rats bearing C6 gliomas, C-LNC (1.5mg/kg/day, i.p.) decreased the tumor size and malignance and prolonged animal survival when compared to same dose of non-encapsulated drug. In addition, serum markers of tissue toxicity and histological parameters were not altered. Considered overall, the data suggest that the nanoencapsulation of curcumin in LNC is an important strategy to improve its pharmacological efficacy in the treatment of gliomas.
在本研究中，我们开发了载姜黄素脂质核纳米胶囊（C-LNCs），以试图提高这种多酚的抗胶质瘤活性。C-LNC显示出纳米技术特性，如纳米级平均尺寸（196nm）、100%的包封率、多分散指数低于0.1以及负的ζ电位。体外释放试验表明姜黄素从脂质核纳米胶囊中可控释放。在C6和U251MG胶质瘤中，C-LNC促进了姜黄素的双相递送：第一个峰值出现在治疗早期（1-3小时），而第二阶段的开始发生在48小时后。在C6细胞中，C-LNC的细胞毒性仅在96小时后与未包封的姜黄素相当，而在U251MG中孵育24小时后，C-LNCs比未包封的姜黄素更具细胞毒性。在C-LNC以及游离姜黄素处理中均观察到G2/M期阻滞和自噬的诱导。在携带C6胶质瘤的大鼠中，与相同剂量的未包封药物相比，C-LNC（1.5mg/kg/天，腹腔注射）减小了肿瘤大小和恶性程度，并延长了动物存活时间。此外，组织毒性的血清标志物和组织学参数未改变。总体而言，数据表明姜黄素在LNC中的纳米包封是提高其在胶质瘤治疗中药理疗效的重要策略。
