Multidrug resistance reversal by co-delivery of tariquidar (XR9576) and paclitaxel using long-circulating liposomes
| Autor: | Patel, Niravkumar R., Rathi, Alok, Mongayt, Dmitriy, Torchilin, Vladimir P. |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Paclitaxel
Surface Properties Antineoplastic Agents Phytogenic Article Drug Resistance Multiple Drug Resistance Neoplasm Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols Liposomes Quinolines Humans Rhodamine 123 ATP Binding Cassette Transporter Subfamily B Member 1 Molecular Targeted Therapy Drug Screening Assays Antitumor Particle Size |
| Popis: | One of the major obstacles to the success of cancer chemotherapy is the multidrug resistance (MDR) often resulting due to the overexpression of drug efflux transporter pumps such as P-glycoprotein (P-gp). Highly efficacious third generation P-gp inhibitors, like tariquidar, have shown promising results in overcoming the MDR. However, P-gp is also expressed in normal tissues like blood brain barrier, gastrointestinal track, liver, spleen and kidney. To maximize the efficacy of P-gp inhibitor and reduce the systemic toxicity, it is important to limit the exposure of P-gp inhibitors and the anticancer drugs to normal tissues and increase their co-localization with tumor cells. In this study, we have investigated the co-delivery of the P-gp inhibitor, tariquidar, and cytotoxic drug, paclitaxel, into tumor cells to reverse the MDR using long-circulating liposomes. Tariquidar- and paclitaxel-loaded long-circulating liposomes showed significant resensitization of the resistant variant for paclitaxel, which could be correlated with an increased accumulation of paclitaxel in tumor cells. These results suggest that the co-delivery of the P-gp inhibitor, tariquidar, and the cytotoxicity inducer, paclitaxel, looks like a promising approach to overcome the MDR. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|