Authors
Marion Paolini1,2, Laurence Poul, PhD1, Audrey Darmon1, Matthieu Germain, PhD1, Agnès Pottier, PhD1, Laurent Levy, PhD1, Eric Vibert, MD, PhD2
1 – Nanobiotix SA, rue de Wattignies, Paris, France
2 – UMR-S 1193 Inserm/University Paris Sud, Centre Hépato-Biliaire, Hôpital Paul Brousse, Villejuif, France
Summary
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.
