(536d) Co-Delivery of Doxorubicin and Paclitaxel Via Multilayer Liposomes for Enhanced Cancer Therapy

Multidrug resistance (MDR) remains a major obstacle in the treatment of cancer by chemotherapy. The combined treatment with two or more drugs was shown to be beneficial in reducing the development of drug resistance by treating tumors at varying stages of their growth cycles and in inducing the therapeutic synergism of combined anticancer drugs. However, it has been reported that the pharmacokinetics and bio-distribution of two drugs is usually different, leading to the uncontrolled drug ratio after bolus injection of simply infusing two drugs. And there is growing evidence that therapeutic effect of drug combination is governed by the drug-to-drug ratio. Thus, controlling the drug ratio at the target site is critical for the desired outcome and may overcome drug resistance. Here, co-encapsulation of different drugs in a single multilayer liposomal formulation is used to better control the drug ratio at the tumor site. Previously, a robust multilayer liposomal delivery system with a slow and sustainable release kinetic profile in serum was investigated in our lab, showing a great potential as a nanocarrier by reducing systemic toxicity and improving therapeutic efficacy. In this study, we demonstrate that multilayer liposomes can co-deliver doxorubicin and paclitaxel at a predetermined ratio that maximize the combination efficacy by overcoming drug resistance and inducing synergistic effect in various tumor cells, including drug resistant tumor cell lines. Moreover, these liposomes demonstrate the ability to maintain the therapeutic effects in vivo and are more effective than cocktail mixture of single-drug-loaded liposomes and the cocktail administration of the free drugs.