title: Oral delivery of insulin via polyethylene imine-based nanoparticles for colonic release allows glycemic control in diabetic rats.
abstract: In this study, insulin-containing nanoparticles were loaded into pellet cores and orally administered to diabetic rats. Polyethylene imine-based nanoparticles, either placebo or loaded with insulin, were incorporated by extrusion and spheronization technology into cores that were subsequently coated with three overlapping layers and a gastroresistant film. The starting and coated systems were evaluated in vitro for their physico-technololgical characteristics, as well as disintegration and release performance. Nanoparticles-loaded cores showed homogeneous particle size distribution and shape. When a superdisintegrant and a soluble diluent were included in the composition enhanced disintegration and release performance were observed. The selected formulations, coated either with enteric or three-layer films, showed gastroresistant and release delayed behavior in vitro, respectively. The most promising formulations were finally tested for their hypoglycemic effect in diabetic rats. Only the nanoformulations loaded into the three-layer pellets were able to induce a significant hypoglycemic activity in diabetic rats. Our results suggest that this efficient activity could be attributed to a retarded release of insulin into the distal intestine, characterized by relatively low proteolytic activity and optimal absorption.
authors.affiliation: Università degli Studi di Milano-Bicocca, NanoBioLab, Dipartimento di Biotecnologie e Bioscienze, piazza della Scienza 2, 20126 Milan, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Salvioni
authors.affiliation: Università degli Studi di Milano, Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", via G.B. Grassi 74, 20157 Milan, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Fiandra
authors.affiliation: Università degli Studi di Milano, Dipartimento di Scienze Farmaceutiche, Sezione di Tecnologia e Legislazione Farmaceutiche "Maria Edvige Sangalli", via G. Colombo 71, 20133 Milan, Italy.
authors.forename: Maria Dorly
authors.initials: MD
authors.lastname: Del Curto
authors.affiliation: Università degli Studi di Milano, Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", via G.B. Grassi 74, 20157 Milan, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Mazzucchelli
authors.affiliation: Università degli Studi di Milano, Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", via G.B. Grassi 74, 20157 Milan, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Allevi
authors.affiliation: Università degli Studi di Milano, Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", via G.B. Grassi 74, 20157 Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Truffi
authors.affiliation: Università degli Studi di Milano, Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", via G.B. Grassi 74, 20157 Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Sorrentino
authors.affiliation: Università degli Studi di Milano-Bicocca, NanoBioLab, Dipartimento di Biotecnologie e Bioscienze, piazza della Scienza 2, 20126 Milan, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Santini
authors.affiliation: Università degli Studi di Milano, Dipartimento di Scienze Farmaceutiche, Sezione di Tecnologia e Legislazione Farmaceutiche "Maria Edvige Sangalli", via G. Colombo 71, 20133 Milan, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Cerea
authors.affiliation: Università degli Studi di Milano, Dipartimento di Scienze Farmaceutiche, Sezione di Tecnologia e Legislazione Farmaceutiche "Maria Edvige Sangalli", via G. Colombo 71, 20133 Milan, Italy. Electronic address: luca.palugan@unimi.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Palugan
authors.affiliation: Università degli Studi di Milano, Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", via G.B. Grassi 74, 20157 Milan, Italy. Electronic address: fabio.corsi@unimi.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Corsi
authors.affiliation: Università degli Studi di Milano-Bicocca, NanoBioLab, Dipartimento di Biotecnologie e Bioscienze, piazza della Scienza 2, 20126 Milan, Italy. Electronic address: miriam.colombo@unimib.it.
authors.forename: Miriam
authors.initials: M
authors.lastname: Colombo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D003692:Delayed-Action Preparations; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D004337:Drug Carriers; D004339:Drug Compounding; D065546:Drug Liberation; D004355:Drug Stability; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D007408:Intestinal Absorption; D053758:Nanoparticles; D010316:Particle Size; D011094:Polyethyleneimine / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013311:Streptozocin; D013997:Time Factors
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D013311:Streptozocin; D011094:Polyethyleneimine
keywords: Insulin release; Multiple-unit formulation; Peptide oral delivery; Polymeric nanoparticles; Type 1 diabetes