title: A novel bottom-up process to produce nanoparticles containing protein and peptide for suspension in hydrofluoroalkane propellants.
abstract: To overcome the disadvantages of microemulsion and nanoprecipitation methods to produce protein-containing nanoparticles, a novel bottom-up process was developed to produce nanoparticles containing the model protein lysozyme. The nanoparticles were generated by freeze-drying a solution of lysozyme, lecithin and lactose in tert-butyl alcohol (TBA)/water co-solvent system and washing off excess lecithin in lyophilizate by centrifugation. Formulation parameters such as lecithin concentration in organic phase, water content in TBA/water co-solvent, and lactose concentration in water were optimized so as to obtain desired nanoparticles with retention of the bioactivity of lysozyme. Based on the results, 24.0% (w/v) of lecithin, 37.5% (v/v) of water content, and 0.56% (w/v) of lactose concentration were selected to generate spherical nanoparticles with approximately 200 nm in mean size, 0.1 in polydispersity index (PI), and 99% retained bioactivity of lysozyme. These nanoparticles rinsed with ethanol containing dipalmitoylphosphatidylcholine (DPPC), Span 85 or oleic acid (3%, w/v) could readily be dispersed in HFA 134a to form a stable suspension with good redispersibility and 98% retained bioactivity of lysozyme. The study indicates there is a potential to produce pressed metered dose inhaler (pMDI) formulations containing therapeutic protein and peptide nanoparticles.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Yinhe
authors.initials: Y
authors.lastname: Tan
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Yang
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Peng
authors.forename: Feng
authors.initials: F
authors.lastname: Xin
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Xu
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.forename: Chunshun
authors.initials: C
authors.lastname: Zhao
authors.forename: Haiyan
authors.initials: H
authors.lastname: Hu
authors.forename: Chuanbin
authors.initials: C
authors.lastname: Wu
mesh_terms: D000280:Administration, Inhalation; D000335:Aerosol Propellants / Q000737:chemistry*; D000890:Anti-Infective Agents / Q000032:analysis / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D005612:Freeze Drying; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D007785:Lactose / Q000737:chemistry; D054709:Lecithins / Q000737:chemistry; D036501:Metered Dose Inhalers; D009113:Muramidase / Q000032:analysis / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010455:Peptides / Q000737:chemistry; D011506:Proteins / Q000737:chemistry; D014867:Water / Q000737:chemistry; D020002:tert-Butyl Alcohol / Q000737:chemistry; D005466:Fluorocarbons
chemical_list: D000335:Aerosol Propellants; D000890:Anti-Infective Agents; D004337:Drug Carriers; D006845:Hydrocarbons, Fluorinated; D007785:Lactose; D054709:Lecithins; D009113:Muramidase; D010455:Peptides; D011506:Proteins; D014867:Water; D020002:tert-Butyl Alcohol; C094049:apaflurane; D005466:Fluorocarbons