Drug Discov Ther. 2015;9(3):205-212. (DOI: 10.5582/ddt.2015.01016)

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

Gao J, Wang Z, Liu H, Wang L, Huang G


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 temozolomideliposomes was in line with First-order kinetics and Weibull equation. The pharmacokinetics study was evaluated by pharmacokinetics parameters. The t1/2β and MRT of temozolomideliposomes were 3.57 times and 1.27 times greater than that of temozolomide solution. The Cmax 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 temozolomideliposomes 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.

KEYWORDS: Temozolomide, liposomes, gliomas, pharmacokinetics, biodistribution

Full Text: