Lecithin-Stabilized Polymeric Micelles (LsbPMs) for Delivering Quercetin: Pharmacokinetic Studies and Therapeutic Effects of Quercetin Alone and in Combination with Doxorubicin

In this study, lecithin-stabilized polymeric micelles (L sb PMs) were prepared to load quercetin (QUE) in order to improve its bioavailability and increase its antitumor activity. Its combination with doxorubicin (DOX) to minimize DOX-mediated cardiac toxicity and increase the antitumor activity of QUE-loaded L sb PMs was also examined. L sb PMs were prepared following a previously reported procedure. Results demonstrated that optimal QUE-loaded L sb PMs contained quercetin, D-α-tocopheryl polyethylene glycol succinate, and lecithin at a weight ratio of 6:40:80. Drug-release studies showed that QUE released from L sb PMs followed a controlled release pattern. A cytotoxicity assay revealed that QUE-loaded L sb PMs had significant anticancer activities against MCF-7, SKBR-3, and MDA-MB-231 human breast cancer cells and CT26 mouse colon cancer cells. In animal studies, intravenous administration of QUE-loaded L sb PMs resulted in efficient growth inhibition of CT26 colon cancer cells in a Balb/c mice model. In a pharmacokinetics study compared to free QUE, intravenous and oral administration of QUE-loaded L sb PMs was found to have significantly increased the relative bioavailability to 158% and 360%, respectively, and the absolute bioavailability to 5.13%. The effect of QUE-loaded L sb PMs in combination with DOX resulted in efficient growth inhibition of CT26 colon cancer cells and reduced cardiac toxicity in the Balb/c mice model.