title: Protein delivery using nanoparticles based on microemulsions with different structure-types.
abstract: Poly(alkylcyanoacrylate) nanoparticles based on microemulsions with different structure-types and containing insulin as a model protein were prepared and characterised in this study. A phase diagram of the pseudoternary system isopropyl myristate, caprylocaproyl macrogolglycerides, polyglycerol oleate and water was established. All compounds used in this study were pharmaceutically acceptable and biocompatible. The area in the phase diagram containing optically isotropic, monophasic systems was designated as the microemulsion region. Systems within this region were identified as water-in-oil (w/o), bicontinuous and oil-in-water (o/w) microemulsions with viscosity, conductivity, differential scanning calorimetry and self-diffusion NMR. The size distributions of the resulting nanoparticles prepared by interfacial polymerisation from selected microemulsions using ethyl (2) cyanoacrylate and butyl (2) cyanoacrylate were unimodal but template- and monomer-dependent and ranged from 160 to 400 nm. Entrapment and release of insulin were also studied. Entrapment ranged from 11.5 to 20.9% and a near zero-order release was observed after an initial burst. Release of insulin was monitored for 6h. Insulin-loaded nanoparticles were 320-350 nm in size. The microemulsion-structure was retained during the polymerisation process as determined by NMR. This study showed that these microemulsions with flexible formulation possibilities for the solubilisation of peptides and proteins depending on their microstructure could serve well as a platform for designing encapsulation processes for oral delivery of insulin.
authors.affiliation: School of Pharmacy, University of Otago, P.O. Box 913, Dunedin, New Zealand. anja.graf@stonebow.otago.ac.nz
authors.forename: Anja
authors.initials: A
authors.lastname: Graf
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Jack
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Whittaker
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Hook
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
mesh_terms: D002152:Calorimetry, Differential Scanning; D003487:Cyanoacrylates / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D004339:Drug Compounding; D004553:Electric Conductivity; D004655:Emulsions; D007328:Insulin / Q000008:administration & dosage; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D010316:Particle Size; D011506:Proteins / Q000008:administration & dosage*; D012995:Solubility; D013329:Structure-Activity Relationship; D013499:Surface Properties; D014783:Viscosity
chemical_list: D003487:Cyanoacrylates; D004337:Drug Carriers; D004655:Emulsions; D007328:Insulin; D011506:Proteins