A new opportunity for nanomedicines: Micellar cytochrome P450 inhibitors to improve drug efficacy in a cancer therapy model.
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 24h 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.
Nanobiotix, France; UMR-S 1193 Inserm/University Paris Sud, Centre Hépato-Biliaire, Hôpital Paul Brousse, Villejuif, France. Electronic address: marion.paolini@nanobiotix.com.
Marion
M
Paolini
Nanobiotix, France.
Laurence
L
Poul
Nanobiotix, France.
Audrey
A
Darmon
Nanobiotix, France.
Matthieu
M
Germain
Nanobiotix, France.
Agnès
A
Pottier
Nanobiotix, France.
Laurent
L
Levy
UMR-S 1193 Inserm/University Paris Sud, Centre Hépato-Biliaire, Hôpital Paul Brousse, Villejuif, France.
Eric
E
Vibert
D000818:Animals; D000970:Antineoplastic Agents; D045744:Cell Line, Tumor; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000008:administration & dosage*; D003577:Cytochrome P-450 Enzyme System; D006801:Humans; D008297:Male; D051379:Mice; D008823:Micelles; D050997:Nanomedicine / Q000379:methods*
D000970:Antineoplastic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D008823:Micelles; D003577:Cytochrome P-450 Enzyme System
Furanocoumarin; Hepatic CYP450; Pharmacoenhancer; Polysorbate 80