Prolonged antidiabetic effect of zinc-crystallized insulin loaded glycol chitosan nanoparticles in type 1 diabetic rats.
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.
Jo
Hyung Gon
HG
Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Korea.
Min
Kyung Hyun
KH
Nam
Tae Hwan
TH
Na
Seong Ju
SJ
Park
Jae Hyung
JH
Jeong
Seo Young
SY
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
D001786:Blood Glucose; D004337:Drug Carriers; D006018:Glycols; D007004:Hypoglycemic Agents; D007328:Insulin; D048271:Chitosan