Mixed micelles of PEG₂₀₀₀-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

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• 作者：Kanwaldeep K. Gill ; Amal Kaddoumi ; Sami Nazzal ; ^{nazzal@ulm.edu}
• 关键词：NSCLC ; non-small cell lung cancer ; P-gp ; P-glycoprotein ; vitamin E-TPGS ; vitamin E-d-alpha tocopheryl polyethyleneglycol succinate ; A549 ; adenocarcinomic human alveolar basal epithelial cells ; NF-魏B ; nuclear factor kappa-light-chain-enhancer of activated
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2012
• 期刊代码：15_09280987
• 类别：pha
• 出版时间：12 May, 2012
• 卷：46
• 期：1-2
• 页码：64-71
• 文件大小：636 K

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 PEG₂₀₀₀-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 IC₅₀ of paclitaxel and parthenolide determined by MTT assay were 108.6 nM and 21 渭M, respectively, while the combination had an IC₅₀ of 64.15 nM in A549 cells. In the taxol resistant cell lines, the IC₅₀ values of paclitaxel and parthenolide were 233 nM and 32 渭M, respectively, while the combination had an IC₅₀ 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.