title: Distribution, transition, adhesion and release of insulin loaded nanoparticles in the gut of rats.
abstract: The purpose of this work was to investigate distribution, transition, bioadhesion and release behaviors of insulin loaded pH-sensitive nanoparticles in the gut of rats, as well as the effects of viscosity agent on them. Insulin was labeled with fluorescein isothiocyanate (FITC). The FITC-insulin solution and FITC-insulin nanoparticle aqueous dispersions with or without hydropropylmethylcellulose (HPMC, 0.2%, 0.4%, or 0.8% (w/v)) were orally administered to rats, respectively. The amounts of FITC-insulin in both the lumen content and the intestinal mucosa were quantified by a spectrofluorimeter. The release profiles in the gut were plotted by the percentages of FITC-insulin released versus time. FITC-insulin nanoparticle aqueous dispersion showed similar stomach but lower intestine empty rates, and enhanced intestinal mucosa adhesion in comparison with FITC-insulin solution. Addition of the HPMC reduced the stomach and intestine empty rates, enhanced the adhesion of FITC-insulin to the intestine mucosa. The release of FITC-insulin from nanoparticles in the gut showed an S-shape profile, and addition of HPMC prolonged the release half-life from 0.77 to 1.51h. It was concluded that the behaviors of pH-sensitive nanoparticles tested in gastrointestinal tract of rats and the addition of HPMC were favorable to the absorption of the drug loaded.
authors.affiliation: School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, Beijing 100083, China.
authors.forename: Ming-Guang
authors.initials: MG
authors.lastname: Li
authors.forename: Wan-Liang
authors.initials: WL
authors.lastname: Lu
authors.forename: Jian-Cheng
authors.initials: JC
authors.lastname: Wang
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Xue-Qing
authors.initials: XQ
authors.lastname: Wang
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: Zheng
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D041981:Gastrointestinal Tract / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D007408:Intestinal Absorption / Q000502:physiology*; D008297:Male; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013552:Swine
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D016650:Fluorescein-5-isothiocyanate