title: Bioadhesive polysaccharide in protein delivery system: chitosan nanoparticles improve the intestinal absorption of insulin in vivo.
abstract: There are many ongoing investigations to improve the oral bioavailability of peptide and protein formulations. Bioadhesive polysaccharide chitosan nanoparticles (CS-NPs) would seem to further enhance intestinal absorption of them. In this study, Insulin-loaded CS-NPs were prepared by ionotropic gelation of CS with tripolyphosphate anions. Its particle size distribution and zeta potential were determined by photon correction spectroscopy and laser Dopper anemometry. The ability of CS-NPs to enhance intestinal absorption of insulin and increase the relative pharmacological bioavailability of insulin was investigated by monitoring the plasma glucose level of alloxan-induced diabetic rats after oral administration of various doses of insulin-loaded CS-NPs. CS-NPs had a particle size in the range of 250-400 nm and its polydispersity index was smaller than 0.1, positively charged, stable. Insulin association was found up to 80% and its in vitro release showed a great initial burst with a pH-sensitivity property. CS-NPs enhanced the intestinal absorption of insulin to a greater extent than the aqueous solution of CS in vivo. Above all, after administration of 21 I.U./kg insulin in the CS-NPs, the hypoglycemia was prolonged over 15 h and the average pharmacological bioavailability relative to SC injection of insulin solution was up to 14.9%.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Pan
authors.forename: Ying-jian
authors.initials: YJ
authors.lastname: Li
authors.forename: Hui-ying
authors.initials: HY
authors.lastname: Zhao
authors.forename: Jun-min
authors.initials: JM
authors.lastname: Zheng
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Gang
authors.initials: G
authors.lastname: Wei
authors.forename: Jin-song
authors.initials: JS
authors.lastname: Hao
authors.forename: Fu-de
authors.initials: FD
authors.lastname: Cui
mesh_terms: D000269:Adhesives / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002686:Chitin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D048271:Chitosan; D016503:Drug Delivery Systems / Q000379:methods*; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D036103:Nanotechnology / Q000379:methods*; D011134:Polysaccharides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000269:Adhesives; D001786:Blood Glucose; D007328:Insulin; D011134:Polysaccharides; D002686:Chitin; D048271:Chitosan