title: Insulin nanoparticles: stability and aerosolization from pressurized metered dose inhalers.
abstract: Nanoparticles containing insulin have been produced by emulsification processes followed by freeze-drying. Purified nanoparticles were suspended in hydrofluoroalkane (HFA) 134a, using essential oils (cineole and citral) as suspension stabilizers to form pressurized metered dose inhaler (pMDI) formulations. The retention of insulin integrity after formulation processing was determined using high performance liquid chromatography (HPLC), size exclusion chromatography (SEC), circular dichroism (CD) and fluorescence spectroscopy. The results indicated that the native structure of insulin was retained after formulation processing. Aerosolization properties of the manufactured pMDI formulations were determined using a multi-stage liquid impinger. The results showed that the nanoparticles were suitable for peripheral lung deposition, with a fine particle fraction (FPF(<1.7 microm)) of approximately 45% (w/w). In conclusion, the pMDI formulations with nanoparticles containing insulin developed in this study have the potential to deliver protein therapeutics via inhalation for systemic action.
authors.affiliation: Pharmaceutics Department, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK.
authors.forename: Bildad K
authors.initials: BK
authors.lastname: Nyambura
authors.forename: Ian W
authors.initials: IW
authors.lastname: Kellaway
authors.forename: Kevin M G
authors.initials: KM
authors.lastname: Taylor
mesh_terms: D000080462:Acyclic Monoterpenes; D000280:Administration, Inhalation; D000335:Aerosol Propellants / Q000737:chemistry; D000336:Aerosols; D002626:Chemistry, Pharmaceutical; D003511:Cyclohexanols / Q000737:chemistry; D000077591:Eucalyptol; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D036501:Metered Dose Inhalers; D039821:Monoterpenes / Q000737:chemistry; D053758:Nanoparticles; D009822:Oils, Volatile / Q000737:chemistry; D010316:Particle Size; D014018:Tissue Distribution; D005466:Fluorocarbons
chemical_list: D000080462:Acyclic Monoterpenes; D000335:Aerosol Propellants; D000336:Aerosols; D003511:Cyclohexanols; D000077591:Eucalyptol; D006845:Hydrocarbons, Fluorinated; D007004:Hypoglycemic Agents; D007328:Insulin; D039821:Monoterpenes; D009822:Oils, Volatile; C094049:apaflurane; D005466:Fluorocarbons; C007076:citral