کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5033173 | 1370008 | 2017 | 9 صفحه PDF | دانلود رایگان |
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 6â²,7â²-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 24Â 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.
To prevent the issue of extensive and variable drug metabolism between individuals, we evaluate a new concept: preparing the body to receive the drug. A nanomedicine inhibiting first-pass metabolism of the drug docetaxel in the liver is injected in tumor xenografted mice prior to the drug to enhance its efficacy.150
Journal: Nanomedicine: Nanotechnology, Biology and Medicine - Volume 13, Issue 5, July 2017, Pages 1715-1723