title: Preparation of itraconazole-loaded liposomes coated by carboxymethyl chitosan and its pharmacokinetics and tissue distribution.
abstract: Liposomes are potential carriers for targeting and controlled drug delivery by the intravenous route. Carboxymethyl chitosan (CMC) is a ramification of chitosan with intrinsic water-solubility. The aim of this study is to prepare itraconazole-loaded liposomes coated by carboxymethyl chitosan (CMC-ITZ-Lips), to evaluate its physico-chemical characteristics and the tissue targeting after being injected intravenously (i.v.). This study uses a film dispersion method to prepare itraconazole-loaded liposomes (ITZ-Lips) prior to coating them with CMC. The concentrations of ITZ in selected organs were determined using reversed-phase high-performance liquid chromatography (HPLC) following i.v. administration of ITZ-Sol, ITZ-Lips, and CMC-ITZ-Lips. CMC-ITZ-Lips had an average diameter of 349.3 ± 18 nm with a zeta potential of -35.71 ± 0.62 mV and the in vitro antifungal activity was not inhibited by the entrapment. The CMC-ITZ-Lips exhibited a longer elimination half life (t(1/2β)) in vivo compared with ITZ-Sol and ITZ-Lips after i.v. injection to mice. The biodistribution in mice was also changed after ITZ was encapsulated in CMC coated liposomes. CMC-ITZ-Lips performed significant lung targeting efficiency with AUC, Te and Re of lung all showed obvious elevation. In this study itraconazole was successfully encapsulated into carboxymethyl chitosan-modified liposomes for application of injection.
authors: The School of Pharmaceutical Science, Shandong University ,  44 Wenhua Xi Lu, Ji'nan, 250012, Shandong Province ,  PR China.
authors: Jinping
authors: J
authors: Wang
authors: Guihua
authors: G
authors: Huang
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D019540:Area Under Curve; D001921:Brain / Q000378:metabolism; D002176:Candida albicans / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D004355:Drug Stability; D005260:Female; D017964:Itraconazole / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D054709:Lecithins / Q000737:chemistry; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D046529:Microscopy, Electron, Transmission; D009206:Myocardium / Q000378:metabolism; D010316:Particle Size; D010949:Plasma / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D055672:Static Electricity; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D000588:Amines; D004337:Drug Carriers; D054709:Lecithins; D008081:Liposomes; C514968:carboxymethyl-chitosan; D017964:Itraconazole; D048271:Chitosan; D002784:Cholesterol; C009317:stearylamine