A microemulsion co-loaded with Schizandrin A–docetaxel enhances esophageal carcinoma treatment through overcoming multidrug resistance

摘要

Abstract Multidrug resistance (MDR) is the major underlying cause of the low 5-year survival rate of esophageal carcinoma. In this study, we developed a novel microemulsion system (SD-ME) co-loaded with docetaxel (DTX) and Schizandrin A, a potent chemotherapeutic agent and a potential drug resistance modulator, respectively. In the physicochemical characterization studies, SD-ME displayed a well-defined spherical shape and size (56.62?±?4.16?nm), a narrow polydispersity index (PDI, 0.132?±?0.002), and a negative surface charge (?19.81?±?3.11?mv). In the cellular uptake studies, SD-ME with a DTX concentration of 30?μg/mL exhibited a 3.9-fold enhancement of DTX internalization in DTX-resistant EC109 (EC109/DDR) cells in comparison to that observed for EC109 cells, and the mechanisms were associated with reducing P-gp expression and inhibiting P-gp ATPease. The half-maximal inhibitory concentrations (IC₅₀) of DTX and SD-ME against EC109/DDR cells were 40.57?±?0.39 and 3.59?±?0.06?μg/mL, respectively. Likewise, the apoptotic rate of EC109/DDR treated with SD-ME increased up to 20-fold compared to that observed with free DTX. In anticancer efficacy studies in vivo, SD-ME markedly retarded the tumor growth of nude mice bearing EC109/DDR tumor xenografts compared with D-ME and free DTX throughout the duration of study. Consequently, mice treated with SD-ME had the highest survival rate (37.5%) during the observation period (70 days). In addition, there were no apparent side effects after the administration of SD-ME. Overall, our study provides evidence for SD-ME as an effective drug delivery system for enhanced MDR tumor treatment.