Ceramide lipid-based nanosuspension for enhanced delivery of docetaxel with synergistic antitumor efficiency

Abstract

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.

Keywords:

• Ceramide
• docetaxel
• lipid-based nanosuspension
• co-delivery
• combination therapy

Declaration of interest

The authors confirm that this article content has no conflict of interest. The project was funded by the National Natural Science Foundation of China (No. 81573368) and the Science and Technology Development Project of Shandong Province (2014GGE27121).