Interface-Enrichment-Induced Instability and Drug-Loading-Enhanced Stability in Inhalable Delivery of Supramolecular Filaments

Filamentous microorganisms traveling in aerosol particles display enhanced deposition and retention in the lungs. Inspired by this shape-related biological effect, we report here on the use of supramolecular filaments as potential inhalable drug carriers within aerosols via jet nebulization. We found that the peptide design and supramolecular stability play a crucial role in the interfacial stability and aerosolization properties of the supramolecular filaments. Monomeric units with a positively charged C-terminus produced filaments with reduced aerosol stability, promoting morphological changes after nebulization. Conversely, having a neutral or negatively charged terminus yielded filaments with enhanced stability, where supramolecular integrity is maintained with only reduced length. Our results suggest that molecular enrichment at the air–liquid interface during nebulization is the primary factor to deplete the monomeric peptide amphiphiles in solution, accounting for the observed morphological disrupt...