科研之友
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摘要
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 Iysozyme. The study indicates there is a potential to produce pressed metered dose inhaler (pMDI) formulations containing therapeutic protein and peptide nanoparticles.
