Drug Encapsulation via Peptide‐Based Polyelectrolyte Complexes

Abstract Peptide‐based polyelectrolyte complexes are biocompatible materials that can encapsulate molecules with different polarities due to their ability to be precisely designed. Here we use UV‐Vis spectroscopy, fluorescence microscopy, and infrared spectroscopy to investigate the encapsulation of model drugs, doxorubicin (DOX) and methylene blue (MB) using a series of rationally designed polypeptides. For both drugs, we find an overall higher encapsulation efficiency with sequences that have higher charge density, highlighting the importance of ionic interactions between the small molecules and the peptides. However, comparing molecules with the same charge density, illustrated that the most hydrophobic sequence pairs had the highest encapsulation of both DOX and MB molecules. The phase behavior and stability of DOX‐containing complexes did not change compared to the complexes without drugs. However, MB encapsulation caused changes in the stabilities of the complexes. The sequence pair with the highest charge density and hydrophobicity had the most dramatic increase in stability, which coincided with a phase change from liquid to solid. This study illustrates how multiple types of molecular interactions are required for efficient encapsulation of poorly soluble drugs and provides insights into the molecular design of delivery carriers.