Background: There has been considerable interest in the use of antimicrobial peptides\n(AMPs) as antimicrobial therapeutics in many conditions including cystic fibrosis (CF). The aim\nof this study is to determine if the prodrugs of AMPs (pro-AMPs) can be delivered to the lung\nby a vibrating mesh nebuliser (VMN) and whether the pro-AMP modification has any effect on\ndelivery. Methods: Physical characteristics of the peptides (AMP and pro-AMP) and antimicrobial\nactivity were compared before and after nebulisation. Droplet size distribution was determined by\nlaser diffraction and cascade impaction. Delivery to a model lung was determined in models of\nspontaneously-breathing and mechanically-ventilated patients. Results: The physical characteristics\nand antimicrobial activities were unchanged after nebulisation. Mean droplet size diameters were\nbelow 5 micro min both determinations, with the fine particle fraction approximately 67% for both peptides.\nApproximately 25% of the nominal dose was delivered in the spontaneously-breathing model for both\npeptides, with higher deliveries observed in the mechanically-ventilated model. Delivery times were\napproximately 170 s per mL for both peptides and the residual volume in the nebuliser was below\n10% in nearly all cases. Conclusions: These results demonstrate that the delivery of (pro-)AMPs to\nthe lung using a VMN is feasible and that the prodrug modification is not detrimental. They support\nthe further development of pro-AMPs as therapeutics in CF.
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