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.

Abstract

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 IC50 of paclitaxel and parthenolide determined by MTT assay were 108.6nM and 21μM, respectively, while the combination had an IC50 of 64.15nM in A549 cells. In the taxol resistant cell lines, the IC50 values of paclitaxel and parthenolide were 233nM and 32μM, respectively, while the combination had an IC(50) of 128nM. 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.

• Authors: Kanwaldeep K Gill, Amal Kaddoumi, Sami Nazzal
• Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 46 Issue 1-2 Pg. 64-71 (May 12 2012) ISSN: 1879-0720 [Electronic] Netherlands
• PMID: 22369858 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antineoplastic Agents, Phytogenic
• Drug Carriers
• Micelles
• Phosphatidylethanolamines
• Sesquiterpenes
• Vitamin E
• 1,2-distearoylphosphatidylethanolamine
• parthenolide
• Polyethylene Glycols
• tocophersolan
• Paclitaxel

Topics

• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, chemistry)
• Antineoplastic Agents, Phytogenic (administration & dosage, chemistry)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, chemistry)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Carriers
• Humans
• Inhibitory Concentration 50
• Lung Neoplasms (drug therapy)
• Magnetic Resonance Spectroscopy
• Micelles
• Paclitaxel (administration & dosage, chemistry)
• Particle Size
• Phosphatidylethanolamines (chemistry)
• Polyethylene Glycols (chemistry)
• Sesquiterpenes (administration & dosage, chemistry)
• Vitamin E (analogs & derivatives, chemistry)