title: Prolonged antidiabetic effect of zinc-crystallized insulin loaded glycol chitosan nanoparticles in type 1 diabetic rats.
abstract: New basal insulin formulation was designed and their structural characteristics were investigated in vitro and biological activities in type 1 diabetic rats. Zinc-crystallized insulin was physically loaded into hydrophobically modified glycol chitosan (HGC) nanoparticles by a dialysis method. The series of insulin-HGC formulations were prepared with different feed weight ratio of insulin to HGC from 0.5:1 to 4:1. The loading contents of insulin and size distribution of insulin-HGCs were characterized, and blood glucose responses were investigated in streptozotocin-induced diabetic rats after single subcutaneous injection of regular insulin and insulin-HGCs. The highest loading efficiency and content were obtained in insulin-HGC when a 1:1 feed weight ratio of insulin to HGC was employed. The hydrodynamic diameter of insulin-HGC nanoparticles were in the range of 200 to 500 nm with narrow size distribution. Insulin-HGC effectively sustained insulin release up to 40% within 12 hours followed by a slower controlled release. Insulin-HGC showed an extended blood glucose lowering effect up to 24 h and provided normal blood glucose levels after oral glucose (1.5 g/kg) load at 24 hours post-injection while regular insulin showed severe hypoglycemia. The prolonged time action profiles and low variability of insulin-HGC formulation resulted in improved blood glucose control in diabetic rats and fulfilled a pattern desirable of a basal insulin.
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Korea.
authors.forename: Hyung Gon
authors.initials: HG
authors.lastname: Jo
authors.forename: Kyung Hyun
authors.initials: KH
authors.lastname: Min
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Nam
authors.forename: Seong Ju
authors.initials: SJ
authors.lastname: Na
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Jeong
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D048271:Chitosan; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004337:Drug Carriers; D006018:Glycols; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D007328:Insulin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D053758:Nanoparticles; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D001786:Blood Glucose; D004337:Drug Carriers; D006018:Glycols; D007004:Hypoglycemic Agents; D007328:Insulin; D048271:Chitosan