Combined Delivery and Anti-Cancer Activity of Paclitaxel and Curcumin Using Polymeric Micelles

Paclitaxel (PTX) is efficacious in treating various solid tumors. However, the severe adverse effects of its present formulation (Cremophor EL and ethanol) and the development of drug resistance by the activation of nuclear factor-kappa B (NF-kappa B) reduce the anti-tumor activities of PTX. Curcumin (Cur) demonstrates anti-tumor activity by means of anti-angiogenesis and induction of apoptosis as well as suppression of the activity of NF-kappa B. Therefore, to improve its antitumor activity and eliminate the toxicity of the commercial formulation of PTX, we prepared biodegradable monomethoxy poly(ethyleneglycol)-poly(epsilon-caprolactone) (MPEG-PCL) micelles to co-deliver PTX and Cur using a solid dispersion method. The mixed PTX and Cur polymeric micelles (PTX-Cur-M) produced were monomorphous micelles of 38 nm in diameter that released PTX and Cur for an extended period of time and induced cell apoptosis in vitro. In addition, the PTX-Cur-M exhibited anti-angiogenic activity in vitro and in vivo. Furthermore, the therapeutic efficacy of PTX-Cur-M in a mouse model of colon cancer was evaluated. PTX-Cur-M micelles produced significantly more inhibition of tumor growth than Cur micelles (Cur-M) and PTX micelles (PTX-M) alone at the same dose (P < 0.05 and P < 0.05, respectively). Immunohistochemical and immunofluorescent analyses demonstrated that PTX-Cur-M enhanced tumor cell apoptosis and inhibited angiogenesis to a greater extent than control treatment. Our data suggested that PTX-Cur-M may have potential clinical applications in cancer therapy.