title: A novel approach to oral delivery of insulin by conjugating with low molecular weight chitosan.
abstract: A new oral delivery system for insulin was developed aiming to improve bioavailability based on a conjugate between insulin and low molecular weight chitosan (LMWC) of narrow molecular weight distribution. The conjugate was synthesized from the reaction between site-specifically modified insulin at the lysine residue of the B-chain and sulfhydryl-modified LMWC. To investigate the effect of MWs of LMWC on oral bioavailability of insulin, various LMWCs (3, 6, 9, and 13k average MW) with narrow MW distribution were used to synthesize LMWC-insulin conjugates. The content of insulin in the LMWC-insulin conjugates was calculated by UV spectrophotometer: 62%, 44%, 38%, and 29% for 3, 6, 9, and 13 kDa LMWC, respectively. The biological activity of insulin in LMWC(6k)-insulin conjugate in vivo was 43 ± 0.7%. LMWC-insulin conjugates after oral administration to diabetic rat models could control blood glucose levels effectively for several hours. Of those conjugates, LMWC(9k)-insulin exhibited the highest pharmacodynamic bioavailability of 3.7 ± 0.3% relative to that of subcutaneously (s.c.) injected insulin (100%).
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
authors.forename: Eunhye
authors.initials: E
authors.lastname: Lee
authors.forename: Jinju
authors.initials: J
authors.lastname: Lee
authors.forename: Sangyong
authors.initials: S
authors.lastname: Jon
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001786:Blood Glucose / Q000378:metabolism; D048271:Chitosan / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D005240:Feasibility Studies; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D008970:Molecular Weight; D051381:Rats
chemical_list: D001786:Blood Glucose; D007328:Insulin; D048271:Chitosan