title: Poly(epsilon-caprolactone)/eudragit nanoparticles for oral delivery of aspart-insulin in the treatment of diabetes.
abstract: Nanoparticles prepared with a blend of a biodegradable polyester (poly(epsilon-caprolactone)) and a polycationic nonbiodegradable acrylic polymer (Eudragit RS) have been used as a drug carrier for oral administration of a short-acting insulin analogue, aspart-insulin. Insulin-loaded nanoparticles, about 700 nm in diameter, encapsulated 97.5% of insulin and were able to release about 70% of their content in vitro in a neutral medium over 24 h. When administered orally to diabetic rats, insulin-loaded nanoparticles (50 IU/kg) decreased fasted glycemia for a prolonged period of time and improved the glycemic response to glucose in a time-dependent manner, with a maximal effect between 12 and 24 h after their administration. In parallel, plasma insulin levels increased. However, higher (100 IU/kg) and lower (25 IU/kg) doses of insulin did not exert any biological effect. It is concluded that polymeric nanoparticles composed of poly(epsilon-caprolactone)/Eudragit RS are able to preserve the biological activity of the insulin analogue aspart-insulin; however, the postprandial peak suppression was prolonged more than 24 h by comparison with regular insulin working only 6-8 h. This effect may be explained by the monomeric configuration of aspart-insulin, which is probably better taken up by the intestinal mucosa than regular insulin.
authors.affiliation: Faculty of Medicine, Institute of Physiology, University of Strasbourg, 67000 Strasbourg, France. christiane.damge@medecine.u-strasbg.fr
authors.forename: Christiane
authors.initials: C
authors.lastname: Damgé
authors.forename: Marie
authors.initials: M
authors.lastname: Socha
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ubrich
authors.forename: Philippe
authors.initials: P
authors.lastname: Maincent
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D003920:Diabetes Mellitus / Q000188:drug therapy*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D016503:Drug Delivery Systems; D004563:Electrochemistry; D005079:Excipients; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D061267:Insulin Aspart; D007441:Intubation, Gastrointestinal; D008297:Male; D053758:Nanoparticles; D011091:Polyesters; D011109:Polymethacrylic Acids; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D005079:Excipients; D007004:Hypoglycemic Agents; D007328:Insulin; D011091:Polyesters; D011109:Polymethacrylic Acids; C016240:polycaprolactone; C038300:methylmethacrylate-methacrylic acid copolymer; D061267:Insulin Aspart