title: Erythropoietin-loaded oligochitosan nanoparticles for treatment of periventricular leukomalacia.
abstract: In this study, a single intraperitoneal injection of erythropoietin (EPO) loaded oligochitosan nanoparticles (epo-NPs) (average diameter 266 nm) was investigated as a treatment for periventricular leukomalacia (PVL). Nanoparticles were fabricated using a gelation technology process. PVL rats models were prepared to examine the therapeutic efficacy of epo-NPs and analyze the mechanism by which epo-NPs protect white matter. The metabolization of epo-NPs in the liver was also investigated. The pathology and behavioral data show that this single injection of a low quantity of epo-NPs had an excellent therapeutic effect on the rat model of PVL. The EPO release curve in phosphate buffered saline solution was a good fit with the zero-order kinetics distribution and was maintained at around 25% in 48 h. In vivo experiments demonstrated that 50 IU/kg epo-NPs had the same effect as a 5000 IU/kg direct injection of free EPO. Nanoparticles prolonged the time course of EPO metabolization in the liver and the stable release of EPO from the nanoparticles kept the plasma concentration of EPO at around 100 IU/ml during the 8-12h post-injection. Therefore, we suggest that oligochitosan based nanoparticles are an effective vehicle for drug delivery.
authors.affiliation: State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Leach
authors.forename: Long
authors.initials: L
authors.lastname: Zhang
authors.forename: Wenjing
authors.initials: W
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.forename: Zhang-Qi
authors.initials: ZQ
authors.lastname: Feng
authors.forename: Nongyue
authors.initials: N
authors.lastname: He
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002626:Chemistry, Pharmaceutical; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry; D048271:Chitosan; D004195:Disease Models, Animal; D004337:Drug Carriers; D004339:Drug Compounding; D004921:Erythropoietin / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D019922:GAP-43 Protein / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007274:Injections, Intraperitoneal; D007969:Leukomalacia, Periventricular / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008099:Liver / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D036103:Nanotechnology; D009844:Oligosaccharides; D010316:Particle Size; D051381:Rats; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D004337:Drug Carriers; D019922:GAP-43 Protein; D009844:Oligosaccharides; C493484:oligochitosan; D004921:Erythropoietin; D002686:Chitin; D048271:Chitosan