Long-circulating methotrexate-loaded liposomes exhibit an antitumor effect on human osteosarcoma in vitro
10.3969/j.issn.2095-4344.2016.30.012
- VernacularTitle:甲氨喋呤长循环脂质体对人骨肉瘤细胞的体外抗瘤活性
- Author:
Yingzhou QIN
;
Han CHEN
;
Yang ZHANG
;
Qiqing ZHANG
;
Lingrong LIU
- Publication Type:Journal Article
- From:
Chinese Journal of Tissue Engineering Research
2016;20(30):4489-4495
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND:Liposomes as a new drug delivery system are characterized by few adverse reactions, no immunogenicity and biodegradation. Furthermore, methotrexate-loaded liposomes can significantly reduce drug toxicity and improve anti-tumor effect. OBJECTIVE:To prepare long-circulating methotrexate-loaded liposomes and to evaluate its antitumor activity in MG-63 in vitro. METHODS:The methotrexate-loaded liposomes were prepared using the film dispersion method, and the long-circulating ones were prepared using the post-insertion method. The initial concentrations of methotrexate were 9.1, 1.82, 0.364 g/L. The ultracentrifugation method and spin column method with Sephadex G-10 or G-50 as packing were employed to separate free drugs from the methotrexate-loaded liposomes. Their recovery, size, morphology, encapsulation efficiency and drug-to-lipid ratio were evaluated. The cytotoxity of the long-circulating methotrexate-loaded liposomes purified with ultracentrifugation method and spin column G-50 method under three dose levels (0, 1, 5, 25 mg/L) were determined by MTS method. RESULTS AND CONCLUSION:According to the recovery rates of three methods, the spin column G-50 method was considered as optimal for the long-circulating methotrexate-loaded liposomes. The long-circulating liposomes were spherical or el ipsoidal under transmission electron microscope, about 200 nm in size. At the certain initial concentration of methotrexate, the encapsulation efficiency and drug-to-lipid ratio of the liposomes purified using the spin column G-50 method were remarkably higher than those purified using the other two methods. At the same mass concentration, the cytotoxity of the liposomes purified with ultracentrifugation or spin column G-50 was significantly higher than that of free methotrexate, and furthermore, the cytotoxity of the liposomes purified with spin column G-50 was higher than that of the liposomes purified with ultracentrifugation method. To conclude, the long-circulating methotrexate-loaded liposomes show a higher antitumor activity than free methotrexate in MG-63 cel s in vitro, providing the basis for further investigation of its antitumor effect on human osteosarcoma in vivo.
