title: Liposome encapsulated of temozolomide for the treatment of glioma tumor: preparation, characterization and evaluation.
abstract: 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(1/2β) and MRT of temozolomide-liposomes 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 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.
authors.affiliation: School of Pharmaceutical Science, Shandong University.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Gao
authors.forename: Zhonglan
authors.initials: Z
authors.lastname: Wang
authors.forename: Honghai
authors.initials: H
authors.lastname: Liu
authors.forename: Longmei
authors.initials: L
authors.lastname: Wang
authors.forename: Guihua
authors.initials: G
authors.lastname: Huang
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D001932:Brain Neoplasms / Q000188:drug therapy*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D005260:Female; D005910:Glioma / Q000188:drug therapy*; D008081:Liposomes / Q000737:chemistry; D008297:Male; D051379:Mice; D011817:Rabbits; D012995:Solubility; D000077204:Temozolomide; D014018:Tissue Distribution
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008081:Liposomes; D003606:Dacarbazine; D000077204:Temozolomide