(M1330-01-05) Mitigation of Doxorubicin-Induced Cardiotoxicity and Chemosensitization Using Combination Phytochemicals in Polymeric Micelles

Purpose: The use of Doxorubicin (DOX), a potent chemotherapeutic agent, is limited due to its cardiotoxicity and resistance. DOX is used as a salvage agent in refractory cancers such as recurrent ovarian cancer in which a majority of patients with Stage III or IV will relapse. Many phytochemicals like Resveratrol, Curcumin, and Quercetin have shown anti-tumor activity along with cardioprotection against Dox-induced cardiotoxicity. However, their poor bioavailability limits their use.

Methods: Polymeric micelles (PMs) were formulated to load these phytochemicals in required molar concentrations at therapeutically relevant doses. The micelles were tested In vitro and in vivo for their cardioprotective and chemosensitization effects.

Results: Both in vitro and in vivo data showed an increase in cardiac protection in PM groups. Similarly, PMs also showed synergy when administered with DOX. One of the micelle groups was also able to demonstrate an increase in chemosensitivity to Dox-Resistant ovarian cancer in mice.

Conclusion: Thus, by utilizing these combination phytochemicals in PMs, we can increase the lifetime cumulative dose limit for DOX through dual mechanisms of cardioprotection and chemosensitization with the added benefit of overcoming DOX resistance in tumor tissue.

Acknowledgements: This project was funded by the National Institute of Health


In Vivo efficacy of mRQ and mRC in Doxurubicin sensitive (A2780) and Doxurubicin Resistant (A2780-ADR) cell line. Dox: Doxurubicin, mRC: Resveratol and Curcumin micelles. mRQ: Resveratol and Quercetin micelles


Pharmacokinetic profile of Phytochemicals in Micelles vs Intraperitoneal solution. mRC: Resveratol and Curcumin micelles. mRQ: Resveratol and Quercetin micelles, Res: Resveratol, Que: Quercetin, Cur: Curcumin


Effect of micelles on Left ventricle ejection fraction of Mice RC: Resveratol and Curcumin micelles. mRQ: Resveratol and Quercetin micelles, Dox: Doxurubicin