Co-delivery of doxorubicin and curcumin by polymeric micelles for improving antitumor efficacy on breast carcinoma

Abstract

To date, combination chemotherapy has become a standard regimen to treat cancer patients. However, combination therapy with drugs having distinct properties such as solubility generally requires use of multiple carriers or solvents, which limits the likelihood of simultaneous delivery. In this work, we used biodegradable poly(ethylene glycol)–poly(ε-caprolactone) (mPEG–PCL) micelles as the co-delivery system to load hydrophilic doxorubicin (Dox) and hydrophobic curcumin (Cur) to achieve combination therapy. The co-encapsulation of Dox and Cur into mPEG–PCL micelles was carried out by a simple self-assembly procedure, which was absent of organic solvents, surfactants and vigorous stirring. The prepared Dox and Cur co-loaded micelles (Dox–Cur-M) were monodisperse with small particle size, high encapsulation efficiency (EE) and sustained release behavior. Furthermore, we found the Dox–Cur-M exhibited remarkable progress in either cytotoxic activities or apoptotic effects compared with Dox-M or Cur-M at equivalent concentrations, which was primarily attributed to enhanced cellular uptake of Dox by Cur. In addition, in a subcutaneous 4T1 breast tumor model in vivo, the Dox–Cur-M was more effective in suppressing tumor growth and spontaneous pulmonary metastasis in comparison with the same dose of Dox-M and Cur-M. In conclusion, micellar co-delivery of Dox and Cur could synergistically potentiate antitumor effects on breast tumor.