Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209-0497, USA.
Int J Pharm. 2010 Apr 15;389(1-2):223-31. doi: 10.1016/j.ijpharm.2010.01.018. Epub 2010 Feb 1.
Previously it was shown that combined low dose treatment of tocotrienols and statins synergistically inhibited the growth of highly malignant +SA mammary epithelial cells in culture. Therefore, the objective of the present work was to prepare and characterize lipid nanoparticles that combined simvastatin and tocotrienol rich fraction (TRF) as potential anticancer therapy. The entrapment of simvastatin in the oily nanocompartments, which were formed by TRF inclusion into the solid matrix of the nanoparticles, was verified by its high entrapment efficiency and the absence of endothermic or crystalline peaks when blends were analyzed by DSC and PXRD, respectively. The release of simvastatin from the nanoparticles in sink conditions was characterized by an initial burst release of approximately 20% in 10h followed by a plateau. No significant change in particle size (approximately 100 nm) was observed after storage for six months. The anticancer activity of the nanoparticles was verified in vitro by observing their antiproliferative effects on malignant +SA mammary epithelial cells. The IC(50) of the reference alpha-tocopherol nanoparticles was 17.7 microM whereas the IC(50) of the simvastatin/TRF nanoparticles was 0.52 microM, which confirmed the potency of the combined treatment and its potential in cancer therapy.
先前的研究表明，三烯生育醇与他汀类药物联合低剂量治疗可协同抑制高度恶性+SA 乳腺上皮细胞在培养中的生长。因此，本工作的目的是制备和表征载有辛伐他汀和富含生育三烯酚（TRF）的脂质纳米粒，作为潜在的抗癌治疗方法。通过差示扫描量热法（DSC）和粉末 X 射线衍射法（PXRD）分析混合物，证实辛伐他汀被包封在由 TRF 包含在内的固体基质形成的油性纳米隔室内，其包封效率很高，并且不存在吸热或结晶峰。在溶出条件下，辛伐他汀从纳米粒中的释放特征是在 10 小时内初始突释约 20%，然后达到平台期。在储存六个月后，粒径（约 100nm）没有明显变化。通过观察纳米粒对恶性+SA 乳腺上皮细胞的抗增殖作用，验证了纳米粒的体外抗癌活性。参考α-生育酚纳米粒的 IC（50）为 17.7µM，而辛伐他汀/ TRF 纳米粒的 IC（50）为 0.52µM，这证实了联合治疗的效力及其在癌症治疗中的潜力。
