Process optimization and synergistic anti-tumor effect of MET and CUR codelivery liposomes with improved drug encapsulation efficiency and stability.

Abstract

Based on improved thin-film dispersion method with an optimized preparation process, elevated encapsulation efficiency and excellent stability of the single-chamber liposome, lip@MET/CUR, were achieved for co-delivery of metformin (MET) and curcumin (CUR). To increase the volume of the hydration chamber and the specific surface area during lipid membrane formation, Tween-80 and glass microspheres were introduced in the preparation process. On this basis, the optimal process parameters for high encapsulation efficiency were screened and determined by combining the analytic hierarchy process (AHP), entropy weight method (EWM), and Box-Behnken response surface optimization. Eventually, the optimal encapsulation efficiencies for MET and CUR were determined to be 46.4% ± 1.3% and 94.1% ± 1.5%, respectively. The lip@MET/CUR exhibited an average particle size of 150 ± 2.5 nm with uniform particle size and good storage stability. In vitro drug release experiments revealed a significant sustained-release characteristic of lip@MET/CUR. Specifically, the cumulative release rate of MET decreased from 96.8% to 57.4% within the initial 2 h. Results from MTT assays and experiments conducted in tumor-bearing mice further demonstrated that lip@MET/CUR was more effective in inhibiting the growth of HepG2 cells and tumors compared to free CUR or lip@CUR. In summary, our findings suggest that the optimized lip@MET/CUR formulation holds great potential as a candidate for investigating the synergistic effects of CUR and MET in tumor treatment.