Mixed micelles of PEG 2000-DSPE and vitamin-E TPGS for concurrent delivery of paclitaxel and parthenolide: Enhanced chemosenstization and antitumor efficacy against non-small cell lung cancer (NSCLC) cell lines

摘要

Concurrent combination of chemotherapeutic drugs is a promising alternative to single-agent therapies in cancer. In the present study, paclitaxel and parthenolide were loaded into mixed micelles and tested against taxol sensitive (A549) and resistant (A549-T24) NSCLC cell lines. Combination chemotherapy was further evaluated by isobologram analyses and combination index calculations. Drugs were loaded into micelles by the film casting method using PEG 2000-DSPE and vitamin E-TPGS. Micelle characterization studies included the determination of particle size, encapsulation efficiency, in vitro release kinetics, as well as 1H NMR analysis. The in vitro release of both drugs was slower from the mixed micelles, which maintained an encapsulation efficiency 95% and chemical stability over a storage period of 45 days. The IC 50 of paclitaxel and parthenolide determined by MTT assay were 108.6 nM and 21 μM, respectively, while the combination had an IC 50 of 64.15 nM in A549 cells. In the taxol resistant cell lines, the IC 50 values of paclitaxel and parthenolide were 233 nM and 32 μM, respectively, while the combination had an IC 50 of 128 nM. The efficacy of paclitaxel and parthenolide against both cell lines significantly increased when the drugs were coencapsulted in mixed micelles. Mixed micelles caused 79% cell death, which was significantly higher than the 46% cell death caused by the drugs in solution against taxol sensitive cell lines. In taxol resistant cell lines, the cell death caused by mixed micelles was 70% as compared to 45% cell death caused by un-encapsulated drugs. Co-encapsulation of parthenolide with paclitaxel in mixed micelles increased the anticancer activity of paclitaxel against resistant and sensitive lung cancer cell lines.