Inclusion of Cationic Amphiphilic Peptides in Fmoc-FF Generates Multicomponent Functional Hydrogels

Peptide building blocks have been recently proposed for the fabrication of supramolecular nanostructures able to encapsulate and in vivo deliver drugs of a different nature. The primary sequence design is essential for nanostructure property modulation, directing and affecting affinity for specific drugs. For instance, the presence of positively charged residues of lysine (K) or arginine (R) could allow improving electrostatic interactions and, in turn, the encapsulation of negatively charged active pharmaceutical ingredients, including nucleic acids. In this context, here, we describe the formulation and the multiscale structural characterization of hybrid cationic peptide containing hydrogels (HGs). In these matrices, the well-known low-molecular-weight hydrogelator, Fmoc-diphenylalanine (Fmoc-FF, Fmoc = fluorenyl methoxycarbonyl), was mixed with a library of cationic amphiphilic peptides (CAPs) differing for their alkyl chain (from C8 to C18) in a 1/1 mol/mol ratio. The structural characterization highlighted that in mixed HGs, the aggregation is guided by Fmoc-FF, whereas the cationic peptides are only partially immobilized into the hydrogelated matrix. Moreover, morphology, stiffness, topography, and toxicity are significantly affected by the length of the alkyl chain. The capability of the hydrogels to encapsulate negative drugs was evaluated using the 5-carboxyfluorescein (5-FAM) dye as a model.