Lecithin-Stabilized Polymeric Micelles (L(sb)PMs) 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.