Synergistic co-delivery of doxorubicin and paclitaxel using multi-functional micelles for cancer treatment

The main purposes of this study are to demonstrate the synergistic anticancer drug systems with the combined doxorubicin (D) and paclitaxel (P) via the aid of cell penetrating and cell targeting moieties for enhancing the cancer therapeutic effect. Firstly, the synergistic effect of combined free drugs (D/P) was investigated to obtain the suitable dose combination for subsequent studies. The combination of free drugs D/P at molar ratio of 1/0.2 shows synergistic therapeutic effect compared with the treatment of a free single drug D or P. Secondly, sustainable release systems of two single drug-loaded micelles, (i) co-delivered D-FOL micelle & P-FOL micelle system and (ii) co-delivered D-TAT/FOL micelle & P-TAT/FOL micelle system, at DIP molar ratio of 1/0.2 were investigated. The results show synergistic effect with the higher efficacy of the TAT/FOL system compared to FOL only system. Finally, a dual D/P-loaded system with sustainable release rate, synergistic drug interaction, selective targeting to cancer cells and high cell penetrating ability was designed. The D/P-TAT/FOL micelles exhibit an IC50 value of 0.172 mu M D/0.043 mu M P, which is much lower than the IC50 values of the single drug-loaded micelles without functionalization (3.873 mu M for D-micelles and 0.790 mu M for P-micelles). Overall, this newly developed dual encapsulation of D and P in the multifunctional carrier would be a promising technology for cancer treatment. (C) 2013 Elsevier B.V. All rights reserved.