title: Oral insulin delivery using nanoparticles based on microemulsions with different structure-types: optimisation and in vivo evaluation.
abstract: The purpose of this study was to optimise entrapment of insulin in poly(alkylcyanoacrylate) nanoparticles prepared from microemulsions with different microstructure containing isopropyl myristate, caprylocaproyl macrogolglycerides, polyglyceryl oleate and insulin solution and to investigate the in vitro release and bioactivity of insulin in nanoparticles dispersed in the microemulsion templates. Entrapment efficiency and release of insulin were studied using a reverse-phase HPLC assay. Morphology of the nanoparticles was examined with scanning electron microscopy. Bioactivity of insulin was studied using a streptozotocin-diabetic rat model. Nanoparticles were spherical with 200-400 nm in size without significant difference between different microemulsion templates, types and amounts of monomer. Entrapment efficiency increased significantly with increasing monomer concentration but decreased with increasing aqueous fraction in the microemulsion template. Insulin loading however, showed an opposite trend. In vitro release profiles of insulin from the nanoparticles dispersed in the microemulsion templates were controlled by the monomer concentration only. In vivo, a consistent and significant hypoglycemic effect over controls was found for up to 36 h depending on the type of monomer. No significant serum insulin levels were detectable. This study showed that the strategy of delivering insulin orally, entrapped in nanoparticles and dispersed in a biocompatible microemulsion is promising and highlights the importance of optimisation studies in combination with in vivo experiments.
authors.affiliation: School of Pharmacy, University of Otago, P.O. Box 913, Dunedin, New Zealand. anja.graf@otago.ac.nz
authors.forename: Anja
authors.initials: A
authors.lastname: Graf
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Hook
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001786:Blood Glucose / Q000187:drug effects; D003487:Cyanoacrylates / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D004337:Drug Carriers / Q000737:chemistry*; D004655:Emulsions / Q000737:chemistry; D004659:Enbucrilate / Q000737:chemistry; D005260:Female; D005989:Glycerides; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018625:Microscopy, Atomic Force; D009226:Myristates / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D009829:Oleic Acids / Q000737:chemistry; D009930:Organic Chemicals / Q000737:chemistry; D010316:Particle Size; D010592:Pharmaceutic Aids / Q000737:chemistry; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D001786:Blood Glucose; D003487:Cyanoacrylates; D004337:Drug Carriers; D004655:Emulsions; D005989:Glycerides; D007328:Insulin; D009226:Myristates; D009829:Oleic Acids; D009930:Organic Chemicals; D010592:Pharmaceutic Aids; C480531:polyglyceryl-6-dioleate; C440220:Labrasol; C008205:isopropyl myristate; C029054:ethyl 2-cyanoacrylate; D004659:Enbucrilate; D005990:Glycerol