title: A novel ligand conjugated nanoparticles for oral insulin delivery.
abstract: In order to enhance the interaction between nanocarrier and gastrointestinal epithelial cells, we developed nanoparticles (NPs) modified with targeting ligand FQSIYPpIK (FQS), which specifically interact with integrin αvβ3 receptor expressing on the intestinal epithelium. The targeting NPs were prepared by coating the insulin-loaded poly(lactide-co-glycolide)-monomethoxy-poly(polyethylene glycol) micelle cores with FQS modified trimethyl chitosan chloride. In in vitro study, the fabricated NPs showed ameliorated drug release profile and improved enzymatic stability compared with micelles alone. In the integrin αvβ3 receptor over-expressed Caco-2 cells model, FQS modified NPs exhibited significantly accelerated intracellular uptake due to the active ligand-receptor mediation. Meanwhile, the targeting NPs also showed enhanced transport across the Caco-2 monolayer cells via both transcellular and paracellular pathways. Besides, orally administered FQS modified NPs produced a prominent hypoglycemic response and an increase of the serum insulin concentration in diabetic rats. Both in vitro and in vivo results demonstrated the FQS peptide modified NPs as promising intestinal cell-targeting nanocarriers for efficient oral delivery of insulin.
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System , Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu , P.R. China.
authors.forename: Chong
authors.initials: C
authors.lastname: Liu
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System , Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu , P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shan
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System , Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu , P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System , Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu , P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhu
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System , Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu , P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Xu
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System , Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu , P.R. China.
authors.forename: Yining
authors.initials: Y
authors.lastname: Xu
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System , Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu , P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D048271:Chitosan; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry; D008024:Ligands; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry*; D051381:Rats
chemical_list: C000614851:(lactide-co-glycolide)-monomethoxy-poly(polyethylene glycol); D004337:Drug Carriers; D007328:Insulin; D008024:Ligands; D008823:Micelles; C118071:N-trimethyl chitosan chloride; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D048271:Chitosan
keywords: Caco-2 cells; integrin αvβ3 receptor; ligand FQSIYPpIK; nanoparticles; oral delivery