Liposomes can achieve a controlled release and an improved bioavailability of water- insoluble drug with minimized side effects. Paclitaxel is an efficient anticancer drug for the treatment of various cancers. However, paclitaxel has a solubility of 0.5 mg/L in water and a low bioavailability of 6.5%. Moreover, paclitaxel is a substrate for p-glycoprotein, which shows a decreased accumulation of drug within the cancer cell expressed by a p-glycoprotein. Therefore, the purpose of this study is to prepare a paclitaxel-loaded liposome and evaluate the effect of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as an inhibitor of p-glycoprotein on the paclitaxel-loaded liposome. The paclitaxel-loaded liposome and TPGS coated paclitaxel-loaded liposome had spherical vesicles, with mean particle size 184.9 ± 18.45 nm with PDI 0.324 ± 0.018 and 282.6 ± 20.41 nm with PDI 0.269 ± 0.013, respectively. Paclitaxel-loaded liposome and TPGS coated paclitaxel-loaded liposome showed a controlled and sustained release of PTX over 72 h. The cellular uptake of paclitaxel from TPGS coated paclitaxel-loaded liposome was a 3.56-fold increase for 2 h and 5.75-fold increase for 4 h compared to that from paclitaxel-loaded liposome in MCF-7/ADR cells, resulting in improved cytotoxicity against MCF-7/ADR cells. Western blot assay revealed the P-gp inhibitory effect of TPGS-coated PTX-liposome. In conclusion, TPGS coated liposome with a sustained releasing capability and the inhibitory effect of p-glycoprotein may be a promising carrier for future applications in cancer therapy.
Bibliographical noteFunding Information:
This work was supported by the Basic Science Research Program ( 2016R1A2B4011294 ) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology .
© 2018 Elsevier B.V.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Organic Chemistry
- Cell Biology