title: Solid lipid nanoparticles of temozolomide: potential reduction of cardial and nephric toxicity.
abstract: The aim of this study was to prepare temozolomide solid lipid nanoparticles (TMZ-SLNs), to evaluate its physiochemical characteristics, and to investigate the specific drug targeting of intravenous (i.v.) injected solid lipid nanoparticles of temozolomide. TMZ-SLNs was prepared by an emulsification and low-temperature solidification method. In vitro drug release was conducted in phosphate-buffered saline (pH 6.8) at 37 degrees C. The concentrations of the temozolomide in selected organs were determined using reversed-phase high-performance liquid chromatography (HPLC) following i.v. administration of the TMZ-SLNs and a temozolomide solution (TMZ-Sol). The results show that the TMZ-SLNs had an average diameter of 65.9+/-11.8nm with a zeta potential of -37.2+/-3.6mV and the in vitro drug release was monitored for up to 3 days, and the release behavior was in accordance with Higuchi-equation. In the tested organs, the AUC/dose and the mean residence times (MRT) of the TMZ-SLNs were much higher and longer than those of the TMZ-Sol, especially in brain and reticuloendothelial cells-containing organs. The AUC ratio of TMZ-SLNs to TMZ-Sol in the brain was the highest among the organs. These results indicated that the SLNs is a promising sustained-release and drug-targeting system for antitumor drugs. It may also allow a reduction in dosage and a decrease in systemic toxicity.
authors.affiliation: Pharmaceutical College, Shandong University, 44 Wen hua Xi Lu, Ji'nan250012, Shandong Province, PR China. hgh2003@126.com
authors.forename: Guihua
authors.initials: G
authors.lastname: Huang
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Xiuli
authors.initials: X
authors.lastname: Bi
authors.forename: Mingjin
authors.initials: M
authors.lastname: Dou
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D003627:Data Interpretation, Statistical; D004337:Drug Carriers; D006331:Heart Diseases / Q000139:chemically induced* / Q000473:pathology; D007275:Injections, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D051379:Mice; D053758:Nanoparticles; D011817:Rabbits; D012995:Solubility; D000077204:Temozolomide; D014018:Tissue Distribution
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004337:Drug Carriers; D003606:Dacarbazine; D000077204:Temozolomide