Curcumin-Loaded Blood-Stable Polymeric Micelles for Enhancing Therapeutic Effect on Erythroleukemia

Curcumin has high potential in suppressing many types of cancer and overcoming multidrug resistance in a multifaceted manner by targeting diverse molecular targets. However, the rather low systemic bioavailability resulted from its poor solubility in water and fast metabolism/excretion in vivo has hampered its applications in cancer therapy. To increase the aqueous solubility of curcumin while retaining the stability in blood circulation, here we report curcumin-loaded copolymer micelles with excellent in vitro and in vivo stability and antitumor efficacy. The two copolymers used for comparison were methoxy-poly­(ethylene glycol)-block-poly­(ε-caprolactone) (mPEG–PCL) and N-(tert-butoxycarbonyl)-l-phenylalanine end-capped mPEG–PCL (mPEG–PCL–Phe­(Boc)). In vitro cytotoxicity evaluation against human pancreatic SW1990 cell line showed that the delivery of curcumin in mPEG–PCL–Phe­(Boc) micelles to cancer cells was efficient and dosage-dependent. The pharmacokinetics in ICR mice indicated that intravenous (i.v.) administration of curcumin/mPEG–PCL–Phe­(Boc) micelles could retain curcumin in plasma much better than curcumin/mPEG–PCL micelles. Biodistribution results in Sprague–Dawley rats also showed higher uptake and slower elimination of curcumin into liver, lung, kidney, and brain, and lower uptake into heart and spleen of mPEG–PCL–Phe­(Boc) micelles, as compared with mPEG–PCL micelles. Further in vivo efficacy evaluation in multidrug-resistant human erythroleukemia K562/ADR xenograft model revealed that i.v. administration of curcumin-loaded mPEG–PCL–Phe­(Boc) micelles significantly delayed tumor growth, which was attributed to the improved stability of curcumin in the bloodstream and increased systemic bioavailability. The mPEG–PCL–Phe­(Boc) micellar system is promising in overcoming the key challenge of curcumin’s to promote its applications in cancer therapy.