Penetrating efficiency of supramolecular hydrogel eye drops: Electrostatic interaction surpasses ligand-receptor interaction

The low drug bioavailability of eye drops challenges the therapy of ocular disorders with high efficacy. One of solutions is to extend the corneal retention and enhance the penetration of drug into cornea. Here we synthesize two fluorophore-conjugated peptide based analogs rich in positive charges (i.e., NBD-FFKK) and with a specific ligand (i.e., NBD-FFRGD), respectively, to visualize their performances in vitro and in vivo. The peptides both can self-assemble into supramolecular hydrogels with the microstructure of nanofibers. The in vitro experiments exhibit that two peptides are both uniformly distributed in cytoplasm, and the intracellular amount of peptide rich in positive charges is significantly larger than that of peptide with a specific ligand. The living corneal fluorescence shows that two peptides enter the corneal stroma within 15 min, and the peptide rich in positive charges is accumulated more extensively throughout the entire cornea, revealing that the supramolecular hydrogel eye drops penetrate the cornea more efficiently via electrostatic interaction than that via ligand-receptor interaction. This work, as a comparative study of supramolecular hydrogel eye drops on penetrating efficiency, indicates a possible direction for the design of eye drops with efficient corneal penetration.