title: Multifunctional polyelectrolyte microparticles for oral insulin delivery.
abstract: Multicomponent insulin-containing microparticles are prepared by layer-by-layer assembly of dextran sulfate and chitosan on the core of protein-polyanion complex with or without protease inhibitors. Oral bioavailability of the encapsulated insulin is improved due to the cumulative effect of each component. A physico-chemical study shows that the particle design allows adjustment of the pH-dependent profile of the insulin release, as well as mucoadhesive properties and Ca(2+) binding ability of the microparticles. Supplementing the microparticles with 2-3% protease inhibitors fully prevents proteolysis of human insulin. The pharmacological effect of microencapsulated insulin in doses 50-100 IU kg(-1) is demonstrated in chronic experiments after oral administration to diabetic rats fed ad libitum.
authors.affiliation: Lomonosov Moscow State University, Department of Chemistry, Leninskiye Gory 1-3, 119991, Moscow, Russia. nbalab2008@gmail.com.
authors.forename: Nadezhda G
authors.initials: NG
authors.lastname: Balabushevich
authors.forename: Mikhail A
authors.initials: MA
authors.lastname: Pechenkin
authors.forename: Elena D
authors.initials: ED
authors.lastname: Shibanova
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Volodkin
authors.forename: Elena V
authors.initials: EV
authors.lastname: Mikhalchik
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001786:Blood Glucose / Q000187:drug effects; D055252:Cell-Derived Microparticles / Q000737:chemistry; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D016264:Dextran Sulfate / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D004573:Electrolytes / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D000071228:Polyelectrolytes; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats
chemical_list: D001786:Blood Glucose; D048271:Chitosan; D016264:Dextran Sulfate; D004573:Electrolytes; D007328:Insulin; D000071228:Polyelectrolytes; D011108:Polymers
keywords: chitosan; insulin; layer-by-layer; microencapsulation; oral drug delivery systems; protease inhibitor