title: Insulin-loaded poly(epsilon-caprolactone) nanoparticles: efficient, sustained and safe insulin delivery system.
abstract: The aim of this work was to develop an efficient, biodegradable, biocompatible and safe controlled release system using insulin-loaded poly(epsilon-caprolactone) (PCL) nanoparticles. The insulin-loaded PCL nanoparticles were prepared by double emulsion method (water-in-oil-in-water) using Pluronic F68 as emulsifier. Using the double emulsion method a high insulin encapsulation efficiency (90.6 +/-1.6%) with a zeta potential of -29 +/-2.7 mV and average particle size of 796 +/-10.5 nm was obtained. Insulin-loaded PCL nanoparticles showed no toxicity to MIN6 cells. Insulin nanoparticles administered subcutaneously and intraperitoneally in rats reduced glycaemia of basal levels after 15 minutes, and presented a sustainable hypoglycemic effect on insulin-dependent type 1 diabetic rats, showing to be more efficient than unencapsulated insulin. Furthermore, these nanoparticles were not hepatotoxic, as evaluated by the effect over liver cell-death and oxidative stress scavenger system in rats. These results suggest that insulin-loaded PCL nanoparticles prepared by water-in-oil-in-water emulsion method are biocompatible, efficient and safe insulin-delivering system with controlled insulin release, which indicates that it may be a powerful tool for insulin-dependent patients care.
authors.affiliation: Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas, Campinas, CEP 13083-881, SP Brazil.
authors.forename: Thiago M
authors.initials: TM
authors.lastname: de Araújo
authors.forename: Zaine
authors.initials: Z
authors.lastname: Teixeira
authors.forename: Helena C
authors.initials: HC
authors.lastname: Barbosa-Sampaio
authors.forename: Luiz F
authors.initials: LF
authors.lastname: Rezende
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Boschero
authors.forename: Nelson
authors.initials: N
authors.lastname: Durán
authors.forename: Nelci F
authors.initials: NF
authors.lastname: Höehr
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000138:chemical synthesis*; D003921:Diabetes Mellitus, Experimental / Q000175:diagnosis / Q000188:drug therapy*; D004058:Diffusion; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D008422:Materials Testing; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
chemical_list: D003692:Delayed-Action Preparations; D007004:Hypoglycemic Agents; D007328:Insulin; D053769:Nanocapsules; D011091:Polyesters; C016240:polycaprolactone; D013311:Streptozocin