| Autor: |
Sarisozen C; Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey., Vural I, Levchenko T, Hincal AA, Torchilin VP |
| Jazyk: |
angličtina |
| Zdroj: |
Drug delivery [Drug Deliv] 2012 Nov; Vol. 19 (8), pp. 363-70. Date of Electronic Publication: 2012 Oct 03. |
| DOI: |
10.3109/10717544.2012.724473 |
| Abstrakt: |
Overexpression of drug efflux pump P-gp is one of the major reasons to cause multidrug resistance (MDR). To overcome P-gp mediated MDR, modulators, so called P-gp inhibitors, can be used to block efflux pump activity. Elacridar is one of the most potent P-gp inhibitors, which can cause irreversible and total P-gp blockage. Elacridar, among with other P-gp inhibitors, can be used in combination with anticancer drugs to enhance the effectiveness of chemotherapy against resistant tumor cells. On the other hand, P-gp is presented in normal tissues, thus non-selective blockage of P-gp can cause undesired side effects. Therefore, it is important to deliver P-gp inhibitor only to the tumor cells (along with anticancer drug) and limit its distribution in the body. In this study, we have developed PEG-PE-based long-circulating ca. 15 nm micelles co-loaded with elacridar and paclitaxel, and investigated their ability to overcome paclitaxel resistance in two cancer cell lines. Vitamin E, a common solubility enhancer for PEG-PE micelles, was found to have a negative effect on both particle size and encapsulation efficiencies. The human MDR1 gene-transfected and thus paclitaxel-resistant MDCKII-MDR1 P-gp overexpressing cells were used for cytotoxicity evaluation. Even though PEG-PE based micelles itself have a potential to enhance the cytotoxicity of paclitaxel, elacridar/paclitaxel-co-loaded micelles demonstrated the highest cytotoxicity compared to both free and micellar paclitaxel. The obtained results suggest that co-loading of paclitaxel and elacridar into micellar drug carriers results in promising preparations capable of overcoming paclitaxel resistance. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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