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.

据报道，卡巴他赛作为微管抑制剂，胸腺醌作为HDAC抑制剂影响p53，STAT3，Bax，BCL-2，p21等重要基因，而NF-κB的下调可能具有抗乳腺肿瘤的活性。然而，不良的水溶性和渗透性阻碍了这些药物向靶部位的递送。为了解决交付难题，开发了卡巴他赛和胸腺嘧啶共载脂球。脂质体是粒径小于150 nm的脂质基自组装体，两种药物的包封率均超过90％。体外药物释放研究表明，从脂球基质中持续扩散控制药物释放，导致粒度随着zeta电位的增加而减小。对MCF-7和MDA-MB-231细胞的细胞毒性研究表明，卡巴他赛和胸腺醌是用于治疗乳腺癌的协同组合物，已通过CompuSyn软件进行了验证。在共聚焦激光扫描显微镜中观察到，快速的细胞内在化可能是由于开发的脂球的功效增强所致。与荧光成像中观察到的组合溶液相比，用这些脂质球处理后，观察到癌细胞形态的急剧变化，例如核碎裂，这是凋亡的标志。细胞周期分析和细胞凋亡研究证实，Sub G1期阻滞增加以及由于细胞凋亡导致的细胞死亡。因此，根据观察到的结果，可以得出结论，卡巴他赛和胸腺醌共同负载的脂球是治疗乳腺癌的有效载体。