Antonow Michelli B, Asbahr Ana Carolina C, Raddatz Paula, Beckenkamp Aline, Buffon Andréia, Guterres Sílvia S, Pohlmann Adriana R
Programa de Pós-Graduação em Nanotecnologia Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre 90610-000, RS, Brazil.
Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, Porto Alegre 91501-970, RS, Brazil.
Mater Sci Eng C Mater Biol Appl. 2017 Jul 1;76:374-382. doi: 10.1016/j.msec.2017.03.099. Epub 2017 Mar 14.
Cancer is a major public health problem in the world, being breast cancer the most frequent cancer affecting women. Despite advances in detection and treatment, mortality rates remain high. Therefore, new approaches for breast cancer treatments are necessary. In this study, our objective was to develop a liquid formulation containing doxorubicin-loaded lipid-core nanocapsules (DOX-LNC), to evaluate the in vitro antiproliferative activity and to determine the nanocapsules uptake by MCF-7 cells. Lipid-core nanocapsules (LNC), blank formulation, and DOX-LNC, proposed treatment, were prepared by self-assembling using the solvent displacement method. Hydrodynamic mean diameters (z-average) were respectively 191±31nm and 230±23nm presenting narrow size distributions. Drug content was 0.102±0.029mgmL with an encapsulation efficiency higher than 90%. Formulations were applied to semiconfluent MCF-7 cells. After 24h, LNC showed no cytotoxicity, while DOX-LNC showed an IC of 4.49 micromolar. After 72h of incubation, DOX-LNC showed an IC of 1.60 micromolar demonstrating a sustained effect. The nanocapsules were internalized by endocytosis mediated by caveolin and by fluid phase endocytosis, which are active transport mechanisms. In conclusion, the liquid formulation containing DOX-LNC showed to be a promising product for the breast cancer treatment opening new avenues for further in vivo studies.
癌症是全球主要的公共卫生问题，乳腺癌是影响女性最常见的癌症。尽管在检测和治疗方面取得了进展，但死亡率仍然很高。因此，需要新的乳腺癌治疗方法。在本研究中，我们的目标是开发一种含有载阿霉素脂质核纳米胶囊（DOX-LNC）的液体制剂，评估其体外抗增殖活性，并确定MCF-7细胞对纳米胶囊的摄取情况。脂质核纳米胶囊（LNC）、空白制剂和DOX-LNC（拟用治疗制剂）采用溶剂置换法自组装制备。流体动力学平均直径（z-平均）分别为191±31nm和230±23nm，粒径分布狭窄。药物含量为0.102±0.029mg/mL，包封率高于90%。将制剂应用于半汇合的MCF-7细胞。24小时后，LNC无细胞毒性，而DOX-LNC的IC50为4.49微摩尔。孵育72小时后，DOX-LNC的IC50为1.60微摩尔，显示出持续的效果。纳米胶囊通过小窝蛋白介导的内吞作用和液相内吞作用内化，这两种都是主动转运机制。总之，含有DOX-LNC的液体制剂显示出有望成为乳腺癌治疗产品，为进一步的体内研究开辟了新途径。
