title: Nanoparticles of quaternized chitosan derivatives as a carrier for colon delivery of insulin: ex vivo and in vivo studies.
abstract: The aim of the present study was to develop insulin nanoparticulate systems by using chitosan (CS), triethylchitosan (TEC) and dimethyl-ethylchitosan (DMEC, a new quaternized derivative of chitosan) for colon delivery. The nanoparticles were prepared by the polyelectrolyte complexation (PEC) method. Particle size distribution, zeta potential and polydispersity index of the nanoparticles were determined using dynamic light scattering technique. Transmission electron microscopy (TEM) was also used to observe the morphology of the nanoparticles. It was found that the nanoparticles carried positive charges and showed a size distribution in the range of 170-270 nm with spherical morphology and smooth surface structure. The amount of insulin loaded into the nanoparticles was determined by measuring the association efficiency and also the content of insulin in the nanoparticles. Insulin loading was found to be more than 80% for all of the nanoparticles. In vitro release studies showed a small burst effect at the beginning and then a sustained release characteristic for 5h. Ex vivo investigations revealed better insulin transport across the colon membrane of rats for nanoparticles made with quaternized derivatives than those made of chitosan. In vivo studies in rats have showed enhanced colon absorption of insulin by using these nanoparticles compared to free insulin in diabetic rats. The insulin absorption from the rat's colon was evaluated by its hypoglycemic effect.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Akbar
authors.initials: A
authors.lastname: Bayat
authors.forename: Farid A
authors.initials: FA
authors.lastname: Dorkoosh
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
authors.forename: Leila
authors.initials: L
authors.lastname: Moezi
authors.forename: Bagher
authors.initials: B
authors.lastname: Larijani
authors.forename: Hans E
authors.initials: HE
authors.lastname: Junginger
authors.forename: Morteza
authors.initials: M
authors.lastname: Rafiee-Tehrani
mesh_terms: D000818:Animals; D048271:Chitosan / Q000031:analogs & derivatives / Q000737:chemistry*; D003106:Colon / Q000378:metabolism; D003692:Delayed-Action Preparations; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D016503:Drug Delivery Systems; D004573:Electrolytes / Q000737:chemistry; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008027:Light; D008297:Male; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012542:Scattering, Radiation
chemical_list: D003692:Delayed-Action Preparations; D004573:Electrolytes; D007004:Hypoglycemic Agents; D007328:Insulin; C530700:dimethylethylchitosan; C502513:triethyl chitosan; D048271:Chitosan