Long-circulating doxorubicin and schizandrin A liposome with drug-resistant liver cancer activity: preparation, characterization, and pharmacokinetic.
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| Abstract |
The selectivity of chemotherapeutic agents for liver cancer is poor. When they kill tumour cells, they produce serious adverse reactions in the whole body and multidrug resistance (MDR) is also a major hurdle in liver cancer chemotherapy. Combination therapy is a useful method for overcoming MDR and reducing toxic and side effects. In this study, we developed a long-circulating codelivery system, in which doxorubicin (DOX) and schizandrin A (SchA) are combined against MCF-7/ADR cells. The DOX-SchA long-circulating liposome (DOX-SchA-Lip) was prepared using ammonium sulphate gradient method. The two drugs were co-encapsulated into the distearoyl phosphatidylethanolamine-polyethylene glycol (DSPE-mPEG2000) liposome and the liposome had an average particle size of (100 ± 3.5) nm and zeta electrical potential of (-31.3 ± 0.5) mV. The average encapsulation rate of DOX was 97.98% and that of SchA was 86.94%. DOX in liposome had good sustained-release effect. The results showed that DOX-SchA-Lip could significantly prolong the half-life (t1/2z) of the DOX and SchA, increase their circulation time in vivo, improve its bioavailability and reduce their side effects. Liposome can effectively induce early apoptosis of HepG2/ADR cells and the cell cycle was blocked in S-phase by DOX-SchA-Lip in a dose-dependent manner. The IC50 of compound liposome to HepG2 and HepG2/ADR were 0.55 μmol/L and 1.38 μmol/L, respectively, which could significantly reverse the resistance of HepG2/ADR and the reversion multiple was 30.28. It was verified that DOX-SchA-Lip can effectively kill tumour cells and reverse MDR.
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| Authors | Shi-Yi Xu, Hui Su, Xing-Yu Zhu, Xue-Ying Li, Jie Li, Xi Chen, Qi Wang, Ruo-Yi Hao, Xue-Ying Yan |
| Journal | Journal of liposome research (J Liposome Res) Vol. 32 Issue 2 Pg. 107-118 (Jun 2022) ISSN: 1532-2394 [Electronic] England |
| PMID | 33555226 (Publication Type: Journal Article) |
| Chemical References |
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