A new opportunity for nanomedicines: Micellar cytochrome P450 inhibitors to improve drug efficacy in a cancer therapy model

作者：Paolini Marion^*; Poul Laurence; Darmon Audrey; Germain Matthieu; Pottier Agnes; Levy Laurent; Vibert Eric

来源：Nanomedicine: Nanotechnology, Biology and Medicine , 2017, 13(5): 1715-1723.

DOI：10.1016/j.nano.2017.03.006

• Pharmacoenhancer
• Hepatic CYP450
• Polysorbate 80
• Furanocoumarin

Nanomedicines are mainly used as drug delivery systems; here we evaluate a new application - to inhibit a drug's metabolism thereby enhancing its effective dose. Micelles containing the natural furanocoumarin 6',7'-dihydroxybergamottin (DHB), a known CYP450 inhibitor, were developed to transiently block hepatic CYP450-mediated drug metabolism and increase the bioavailability of the oncology drug docetaxel. Administered in mice 24 h prior to the drug, DHB-micelles enhanced antitumor efficacy in the tumor xenograft models HT-29 and MDA-MB-231, when compared to the drug alone. These DHB-micelles have similar composition to marketed docetaxel-micelles for human use. Despite not being optimized in terms of targeting hepatocytes, they do represent the first injectable example of nanosized metabolism-blocking agents and open the way for further work on such nanomedicines in man.

• 出版日期2017-7