Ceramide lipid-based nanosuspension for enhanced delivery of docetaxel with synergistic antitumor efficiency.
Ceramide lipid-based nanosuspension for enhanced delivery of docetaxel with synergistic antitumor efficiency.
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基于神经酰胺脂质的纳米混悬剂可增强多西紫杉醇的递送并具有协同抗肿瘤效率
DOI：
10.1080/10717544.2016.1225853
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发表时间：
2017-11
期刊：
影响因子：
6
通讯作者：
Zhang N
中科院分区：
文献类型：
--
作者：
Wang T;Feng L;Yang S;Liu Y;Zhang N
神经酰胺（CE）是一种具有肿瘤抑制作用的生物活性脂质，已被广泛用作肿瘤治疗的药物载体和促进剂。以CE为基础的联合治疗在肿瘤治疗中具有吸引力。在我们以前的研究中，CE和多西他赛（DTX）的组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CE脂质基纳米混悬剂（LNS）用于递送DTX以表现出协同治疗作用。评价载药CE-LNS（CE + DTX-LNS）的增强释药和协同治疗作用。CE + DTX-LNS呈球形或椭球形，粒径分布均匀（108.1 ± 3.8 nm），体外释放稳定性好。与CE-LNS + DTX-LNS相比，CE + DTX-LNS能有效地将CE和DTX共定位于同一肿瘤细胞中，并随后发挥协同的细胞损伤作用（p < 0.05）。体内荧光成像结果显示CE + DTX-LNS能有效延长体内循环时间，增强肿瘤部位蓄积。此外，在B16小鼠黑色素瘤模型中观察到的CE + DTX-LNS的抗肿瘤效力为93.94 ± 2.77%，分别显著高于CE-LNS、DTX-LNS、Duopafei®（p < 0.01）和CE-LNS + DTX-LNS（p < 0.05），表明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可见的组织毒性。因此，CE-LNS可以有效地递送DTX，并且由于CE和DTX的共定位，CE + DTX-LNS表现出协同抑制肿瘤生长。CE-LNS有望成为以CE为基础的联合化疗的理想载体。
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.
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