Amphiphilic β-sheet peptides decorated by acidic amino acids may spontaneously assemble into ordered monolayers at interfaces as well as form hydrogels at near physiological pH values. Here we monitored interactions between the peptide Pro-Asp-(Phe-Asp)(5)-Pro and the mildly amphiphilic chemotherapeutic drug doxorubicin (Dox). The peptide in the form of monolayers at the air water interface was found to enhance Dox adsorption, pointing to favorable interactions between the amphiphilic peptide and Dox. In solutions the fluorescence emission of Dox which was fitted to the Stern-Volmer quenching models suggested the formation of Dox associated forms >25 μM and larger forms at >100 μM. In presence of the peptide these larger associated forms appeared already at Dox concentrations >50 μM, indicating enhanced interactions between Dox and the peptide in the β-sheet conformation. Peptide hydrogels loaded with the drug showed sustained release profiles over several days. Smaller fractions of the drug were released with increase in either peptide or initially loaded drug concentrations. The released Dox was found to retain its cytotoxic activity in vitro. This study provides insights on the interactions between the amphiphilic and acidic peptide and Dox that are useful for the bottom up development of Dox-loaded peptide hydrogels for local drug delivery applications.
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