In vitro aerosol delivery and regional airway surface liquid concentrationof a liposomal cationic peptide

A liposome encapsulation was optimized for the entrapment and aerosol deliv ery of an alpha -helical cationic peptide, CM3, which had shown good antimi crobial and antiendotoxin activity in vitro. The encapsulation procedure an d the phospholipids used were selected to maximize both the encapsulation a nd nebulization efficiencies, without compromising liposomal integrity duri ng nebulization. The best compromise was found with dimyristoyl phosphatidy lcholine and dimyristoyl phosphatidylglycerol (3:1 molar ratio), which allo wed for peptide encapsulation levels of 730 mug/mL using 30 MM lipid concen tration. The aerosol produced with the selected liposomal formulation was s ubsequently analyzed for determination of size distribution and nebulizer e fficiencies. These quantities were used as input for a mathematical lung de position model, which predicted local lung depositions of the liposomal pep tides for three models of lung geometry and breathing patterns: an adult, a n 8-year-old child, and a 4-year-old child. The deposition results were the n applied to a novel model of airway surface liquid in the lung to assess t he concentration of the deposited peptide. The resulting concentration esti mates indicate that the minimum inhibitory levels of CM3 can be reached ove r most part of the tracheobronchial region in the adult model, and can be e xceeded throughout the same region in both pediatric model subjects, using a valved jet nebulizer with a 2.5mL volume fill. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association.