The aim of this study was to develop and characterize the paclitaxel (PTX)-lapatinib (LPT) loaded micelles for simultaneous delivery against metastatic breast cancer. Efflux pump-mediated drug resistance influences the efficacy of chemotherapeutic regimens. However, in the newly developed delivery system, LPT was selected to act as chemosensetizer. LPT increases the intracellular level of PTX by inhibition of efflux pumps. Pluronic F127 was selected for the preparation of the micelles, and its critical micelle concentration was determined to be 0.012 mg/ml. D-optimal design was used to analyze the impact of different experimental parameters on PTX and LPT encapsulation ratio. PTX encapsulation ratio was optimized at 68.3%, while LPT encapsulation ratio found to be 70.1%. Transmission electron microscope analyses demonstrate that micelles possess a good core-shell structure without any sharp edge. Laser scattering method results indicated that size of the optimized micelles is 64.81 nm with acceptable polydispersity index (0.309). In vitro release studies showed a sustain release pattern. PTX-LPT-loaded micelles suppressed the proliferation of resistant T-47D cell line (IC = 0.6 ± 0.1 µg/ml) compared to binary mixture of PTX and LPT (IC = 6.7 ± 1.2 µg/ml). Therefore, it is concluded that the developed formulation might increase the therapeutic efficacy in drug resistant metastatic breast cancer.
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