Cell-penetrating peptide conjugated nanoparticle with antioxidant for hearing loss therapy

Abstract

Nowadays, drug delivery carrier for hearing loss therapy has been researched actively. Intratympanic route is the safest way of hearing loss therapy. When attach drug delivery carrier contained hydrogel to the round window membrane, drug diffuses into inner ear. In this study, amphiphilic nanocarrier was synthesized and analyzed, and applied to hair cell of inner ear. The nanocarrier was achieved by conjugating alpha-lipoic acid (LA) and $Arg_8$ to octadecyl grafted poly (2-hydroxyethyl aspartamide) (PHEA) ($PHEA-g-C_{18}-NH_2) backbone, forming a spherical micelle. LA is hydrophobic antioxidant, which was used as a drug for inner ear. $Arg_8$ is a cell-penetrating peptide. The structures of the nanocarrier were analyzed using transmission electron microscopy (TEM), nuclear magnetic resonance (NMR), and dynamic light scattering (DLS). Also, release behavior of LA and critical aggregation concentration (CAC) was confirmed. Through LDH assay and confocal laser scanning microscopy (CLSM), cell uptake property was evaluated. These features suggest that $PHEA-g-C_{18}-Arg_8-LA$ can be a promising drug delivery carrier for hearing loss therapy.