The processing of nanoparticles containing protein for suspension in hydrofluoroalkane propellants.
Nanoparticles delivered from pressurized metered dose inhalers (pMDIs) potentially offer a means of efficiently delivering proteins to the lung. Nanoparticles containing the model protein lysozyme have been produced using microemulsion and nanoprecipitation methods. Freeze-drying water in oil emulsions, with chloroform as the organic solvent, followed by washing of excess surfactant (lecithin) led to the production of lactose nanoparticles having approximately 300 nm mean size. Substitution of lactose with lysozyme led to a significant increase in the mean size of nanoparticles (645-750 nm). This may have been due to the surface activity of lysozyme which altered the emulsification properties. The retained biological activity of lysozyme increased with increased lactose concentration in the formulation, and approximately 99% biological activity was retained when 20% (w/w) lactose was used. Ethanol used in the formulation in place of chloroform changed the production process from emulsification to nanoprecipitation. A monodisperse system (mean size approximately 275 nm, polydispersity index approximately 0.1) of spherical nanoparticles containing 80% (w/w) bioactive lysozyme (retained activity 99%) was generated. The nanoparticles washed with ethanol containing DPPC, oleic acid or Span 85 (2%, w/v) could readily be dispersed in HFA 134a without further processing, and a stable suspension was formed. Lysozyme remained stable (retained biological activity 98%) even after the nanoparticles were suspended in HFA 134a. This indicates the potential of nanoparticles for delivery of proteins from HFA-based pressurized metered dose inhaler formulations.
Pharmaceutics Department, The School of Pharmacy, University of London, 29-39 Brunswick Square, London, UK.
Bildad K
BK
Nyambura
Ian W
IW
Kellaway
Kevin M G
KM
Taylor
D000335:Aerosol Propellants / Q000737:chemistry* / Q000378:metabolism; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D013535:Suspensions; D005466:Fluorocarbons
D000335:Aerosol Propellants; D006845:Hydrocarbons, Fluorinated; D011506:Proteins; D013535:Suspensions; C094049:apaflurane; D005466:Fluorocarbons