Wang Tianqi, Feng Lixia, Yang Shaomei, Liu Yongjun, Zhang Na
a School of Pharmaceutical Science, Shandong University , Ji'nan , People's Republic of China.
Drug Deliv. 2017 Nov;24(1):800-810. doi: 10.1080/10717544.2016.1225853.
Ceramide (CE), a bioactive lipid with tumor suppression, has been widely used as a drug carrier and enhancer for cancer therapy. CE-based combination therapy was prone to be attractive in cancer therapy. In our previous study, the combination of CE and docetaxel (DTX) was proved to be an effective strategy for cancer therapy. To further improve the antitumor efficiency of DTX, the CE lipid-based nanosuspensions (LNS) was prepared for the delivery of DTX to exhibit synergistic therapeutic effect. The enhanced delivery and synergistic therapeutic effect of DTX-loaded CE-LNS (CE + DTX-LNS) were evaluated. CE + DTX-LNS exhibited spherical or ellipsoidal shape, uniform particle size distribution (108.1 ± 3.8 nm), sustained release characteristics and good stability in vitro. Notably, CE + DTX-LNS could effectively co-localize CE and DTX into same tumor cell and subsequently play synergistic cell damage effect compared with CE-LNS + DTX-LNS (p < 0.05). The in vivo fluorescence imaging results showed that CE + DTX-LNS could effectively prolong the in vivo circulation time and enhance the accumulation in tumor sites. Moreover, the antitumor efficacy of CE + DTX-LNS observed in B16 murine melanoma model was 93.94 ± 2.77%, significantly higher than that of CE-LNS, DTX-LNS, Duopafei® (p < 0.01) and CE-LNS + DTX-LNS (p < 0.05), respectively, demonstrating that co-delivery of CE and DTX into same tumor cell was the basis for enhanced synergistic therapeutic effect. Furthermore, histological examination of Blank-LNS showed no visible tissue toxicity compared to normal saline. Consequently, CE-LNS could effectively delivery DTX and CE + DTX-LNS exhibit synergistic inhibition of tumor growth due to the co-localization of CE and DTX. CE-LNS hold great potential to be an appropriate carrier for CE-based combination chemotherapy.
神经酰胺（CE）是一种具有肿瘤抑制作用的生物活性脂质，已被广泛用作癌症治疗的药物载体和增强剂。基于CE的联合疗法在癌症治疗中容易受到关注。在我们之前的研究中，CE与多西他赛（DTX）的联合被证明是一种有效的癌症治疗策略。为了进一步提高DTX的抗肿瘤效率，制备了基于CE脂质的纳米混悬液（LNS）用于递送DTX，以发挥协同治疗作用。评估了负载DTX的CE-LNS（CE + DTX-LNS）的增强递送和协同治疗效果。CE + DTX-LNS呈现球形或椭圆形，粒径分布均匀（108.1±3.8 nm），具有体外缓释特性和良好的稳定性。值得注意的是，与CE-LNS + DTX-LNS相比，CE + DTX-LNS能够有效地将CE和DTX共定位到同一肿瘤细胞中，随后发挥协同细胞损伤作用（p < 0.05）。体内荧光成像结果表明，CE + DTX-LNS能够有效地延长体内循环时间并增强在肿瘤部位的蓄积。此外，在B16小鼠黑色素瘤模型中观察到CE + DTX-LNS的抗肿瘤疗效为93.94±2.77%，分别显著高于CE-LNS、DTX-LNS、多帕菲®（p < 0.01）和CE-LNS + DTX-LNS（p < 0.05），表明将CE和DTX共递送至同一肿瘤细胞是增强协同治疗效果的基础。此外，与生理盐水相比，空白LNS的组织学检查未显示明显的组织毒性。因此，CE-LNS能够有效地递送DTX，并且由于CE和DTX的共定位，CE + DTX-LNS对肿瘤生长具有协同抑制作用。CE-LNS极具潜力成为基于CE的联合化疗的合适载体。
