title: Nanoparticulate delivery system for insulin: design, characterization and in vitro/in vivo bioactivity.
abstract: Insulin-loaded alginate-dextran nanospheres were prepared by nanoemulsion dispersion followed by triggered in situ gelation. Nanospheres were characterized for mean size and distribution by laser diffraction spectroscopy and for shape by transmission electron microscopy. Insulin encapsulation efficiency and in vitro release were determined by Bradford protein assay and bioactivity determined in vitro using a newly developed Western blot immunoassay and in vivo using Wistar diabetic rats. Nanospheres ranged from 267 nm to 2.76 microm in diameter and demonstrated a unimodal size distribution. Insulin encapsulation efficiency was 82.5%. Alginate-dextran particles suppressed insulin release in acidic media and promoted a sustained release at near neutral conditions. Nanoencapsulated insulin was bioactive, demonstrated through both in vivo and in vitro bioassays.
authors.affiliation: Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Rua do Norte, 3000-295 Coimbra, Portugal. catarinareis@ci.uc.pt
authors.forename: Catarina Pinto
authors.initials: CP
authors.lastname: Reis
authors.forename: António J
authors.initials: AJ
authors.lastname: Ribeiro
authors.forename: Simone
authors.initials: S
authors.lastname: Houng
authors.forename: Francisco
authors.initials: F
authors.lastname: Veiga
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Neufeld
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D015153:Blotting, Western; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D016264:Dextran Sulfate / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000097:blood; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D007834:Lasers; D008297:Male; D046529:Microscopy, Electron, Transmission; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012542:Scattering, Radiation; D012995:Solubility; D013678:Technology, Pharmaceutical; D013997:Time Factors
chemical_list: D000464:Alginates; D001786:Blood Glucose; D004337:Drug Carriers; D006603:Hexuronic Acids; D007004:Hypoglycemic Agents; D007328:Insulin; D020723:Glucuronic Acid; D016264:Dextran Sulfate