Derivatives of fullerene (C60) as photosensitizers have rarely been studied as delivery carrier materials. The focus of this study was to explore the potential advantages of diadduct malonic acid-fullerene (DMA-C60) as delivery carrier materials and combination of chemo-phototherapy of some tumors. In this study, DMA-C60 and docetaxel (DTX) were coentrapped in micelles (MCs) (DMA-C60/DTX-MC). The addition of DMA-C60 could obviously improve static stability and decrease critical MC concentration of DTX-MC without hemolysis. The sustained release of DTX and DMA-C60 could be achieved, following Higuichi and first-order model, respectively. DMA-C60 could still produce reactive oxygen species efficiently in HeLa cells after encapsulation in MC. The addition of DMA-C60 under irradiation caused DTX-MC more stronger cytotoxicity, cell cycle changes, and more early apoptotic cells in vitro. More importantly, after intravenous injection, the addition of DMA-C60 in DTX-MC could result in 2.25-fold and 4.57-fold longer mean residence time compared with DTX-MC and Duopafei(®) , increase drug intratumoral distribution and decrease drug distribution in heart and kidney, and enhance antitumor effect under irradiation without body weight loss. These results suggested tremendous promise of DMA-C60 as carrier materials of MC and significant advantages in combination of chemo-phototherapy of some tumors. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3225-3234, 2014.
Keywords: antitumor effect; cancer chemotherapy; cellular mechanisms; controlled release/delivery; diadduct malonic acid-fullerene; excipients; micelles; pharmacokinetics; photosensitive.
© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.