title: Surface functional modification of self-assembled insulin nanospheres for improving intestinal absorption.
abstract: In this work we fabricated therapeutic protein drugs such as insulin as free-carrier delivery system to improve their oral absorption efficiency. The formulation involved self-assembly of insulin into nanospheres (INS) by a novel thermal induced phase separation method. In consideration of harsh environment in gastrointestinal tract, surface functional modification of INS with ɛ-poly-L-lysine (EPL) was employed to form a core-shell structure (INS@EPL) and protect them from too fast dissociation before their arriving at target uptake sites. Both INS and INS@EPL were characterized as uniformly spherical particles with mean diameter size of 150-300 nm. The process of transient thermal treatment did not change their biological potency retention significantly. In vitro dissolution studies showed that shell cross-linked of INS with EPL improved the release profiles of insulin from the self-assembled nanospheres at intestinal pH. Confocal microscopy visualization and transport experiments proved the enhanced paracellular permeability of INS@EPL in Caco-2 cells. Compared to that of INS, enteral administration of INS@EPL at 20 IU/kg resulted in more significant hypoglycemic effects in diabetic rats up to 12 h. Accordingly, the results indicated that surface functional modification of self-assembled insulin nanospheres with shell cross-linked polycationic peptide could be a promising candidate for oral therapeutic protein delivery.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China. Electronic address: kaishi_syphu@hotmail.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Shi
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Pharmacology, School of Life Science and Bio-pharmaceutics, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Kan
authors.affiliation: Department of Pharmacology, School of Life Science and Bio-pharmaceutics, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, School of Life Science and Bio-pharmaceutics, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Gan
authors.affiliation: Department of Pharmacology, School of Life Science and Bio-pharmaceutics, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China. Electronic address: liu306608@sohu.com.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002460:Cell Line; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D008297:Male; D054118:Nanospheres / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013552:Swine; D014961:X-Ray Diffraction
chemical_list: D001786:Blood Glucose; D007328:Insulin
keywords: Insulin; Nanospheres; Self-assembly