Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad, 500037, India.
Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad, 500037, India.
Chem Phys Lipids. 2019 Nov;224:104707. doi: 10.1016/j.chemphyslip.2018.11.009. Epub 2018 Dec 4.
Cabazitaxel as microtubule inhibitor and thymoquinone as HDAC inhibitor affects the important genes like p53, STAT3, Bax, BCL-2, p21 and down regulation of NF-κB are reported for potential activity against breast tumors. However, poor aqueous solubility and permeability hinders the delivery of these drugs to target site. To address the delivery challenges cabazitaxel and thymoquinone co-loaded lipospheres were developed. Lipospheres are the lipid based self-assemblies of particle size below 150 nm were prepared with more than 90% entrapment efficiency for both the drugs. In vitro drug release studies revealed there was a sustained diffusion controlled drug release from liposphere matrix leading to decrease in particle size with increase in zeta potential. Cytotoxicity studies on MCF-7 and MDA-MB-231 cells demonstrated cabazitaxel and thymoquinone as synergistic combination for the treatment of breast cancer which was proved by CompuSyn software. Enhanced efficacy of developed lipospheres can be due to rapid cellular internalization which was observed in confocal laser scanning microscopy. Drastic changes in cancer cell morphology such as nuclear fragmentation were observed upon treatment with these lipospheres in comparison to combination solution as observed in fluorescent imaging which are the hall marks of apoptosis. Cell cycle analysis and apoptosis studies confirmed the increased Sub G1 phase arrest as well as cell death due to apoptosis. Thus, as per observed results, it can be concluded that cabazitaxel and thymoquinone co-loaded lipospheres are the efficient delivery vehicles in management of breast cancer.
卡巴他赛作为微管抑制剂和姜黄素作为组蛋白去乙酰化酶抑制剂，据报道，其对重要基因（如 p53、STAT3、Bax、BCL-2、p21）具有潜在的活性，可下调 NF-κB，因此对乳腺癌具有潜在的治疗作用。然而，较差的水溶性和通透性阻碍了这些药物向靶部位的传递。为了解决这些药物的传递挑战，卡巴他赛和姜黄素共载脂质体被开发出来。脂质体是粒径小于 150nm 的基于脂质的自组装体，对两种药物的包封效率均超过 90%。体外药物释放研究表明，脂质体基质中存在持续的扩散控制药物释放，导致粒径随着 zeta 电位的增加而减小。MCF-7 和 MDA-MB-231 细胞的细胞毒性研究表明，卡巴他赛和姜黄素联合使用是治疗乳腺癌的协同组合，这一结果通过 CompuSyn 软件得到了证实。开发的脂质体的疗效增强可能是由于观察到的快速细胞内化，这在共聚焦激光扫描显微镜中观察到。与联合溶液相比，用这些脂质体处理后观察到癌细胞形态发生剧烈变化，如核碎片，这是细胞凋亡的标志。细胞周期分析和凋亡研究证实，由于细胞凋亡，Sub G1 期阻滞和细胞死亡增加。因此，根据观察到的结果可以得出结论，卡巴他赛和姜黄素共载脂质体是管理乳腺癌的有效递药载体。
