Liposome encapsulated of temozolomide for the treatment of glioma tumor: preparation, characterization and evaluation

被引:87
作者
Gao, Jinhua [1 ]
Wang, Zhonglan [1 ]
Liu, Honghai [2 ]
Wang, Longmei [1 ]
Huang, Guihua [1 ]
机构
[1] Shandong Univ, Sch Pharmaceut Sci, 44 Wenhua Xi Rd, Jinan, Shandong, Peoples R China
[2] Food & Drug Adm Dezhou, Dezhou, Shandong, Peoples R China
关键词
Temozolomide; liposomes; gliomas; pharmacokinetics; biodistribution;
D O I
10.5582/ddt.2015.01016
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Temozolomide plays a critical role in curing glioma at present. The purpose of this work was to develop a suitable drug delivery system which could prolong the half-life, improve the brain targeting, and reduce the systemic effect of the drug. Temozolomide-liposomes were formulated by the method of proliposomes. They were found to be relatively uniform in size of 156.70 +/- 11.40 nm with a narrow polydispersity index (PI) of 0.29 +/- 0.04. The average drug entrapment efficiency and loading capacity were 35.45 +/- 1.48% and 2.81 +/- 0.20%, respectively. The pH of temozolomide-liposomes was 6.46. In vitro release studies were conducted by a dynamic dialysis. The results showed that temozolomide released slowly from liposomes compared with the solution group. The release behavior of temozolomide-liposomes was in line with First-order kinetics and Weibull equation. The pharmacokinetics study was evaluated by pharmacokinetics parameters. The t(1/2 beta) and MRT of temozolomide-liposomes were 3.57 times and 1.27 times greater than that of temozolomide solution. The C-max and AUC values of temozolomide-liposomes were 1.10 times and 1.55 times greater than that of temozolomide solution. The results of pharmacokinetics study showed temozolomide-liposomes prolonged the in vivo circulation time and increased AUC. Furthermore, the biodistribution in mice showed that temozolomide-liposomes preferentially decreased the accumulation of temozolomide in heart and lung and increased the drug concentration in brain after i.v. injection, which implied that temozolomide-liposomes improved the therapeutic effect in the brain and reduced the toxicity in lung and heart.
引用
收藏
页码:205 / 212
页数:8
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