d-arg-dmt-lys-phe-nh2 and Hearing-Loss

Aminoglycoside-induced hearing loss stems from damage or loss of mechanosensory hair cells in the inner ear. Intrinsic mitochondrial cell death pathway plays a key role in that cellular dysfunction for which no proven effective therapies against oto-toxicities exist. Therefore, the aim of the present study was to develop a new mitochondrial targeting drug delivery system (DDS) that provided improved protection from gentamicin. Particularly, SS-31 peptide-conjugated geranylgeranylacetone (GGA) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles were constructed successfully via emulsion-solvent evaporation method. The zebrafish lateral line sensory system was used as an in vivo evaluating platform to investigate the protective efficiency against gentamicin. SS-31 modification significantly reduced the activity of mechanoelectrical transduction (MET) channel and gentamicin uptake in zebrafish lateral line hair cells. As expected, SS-31 conjugated nanoparticles showed mitochondrial specific accumulation in hair cells when compared with unconjugated formulations. Furthermore, intracellular SS-31 modified PLGA NPs slightly enhanced mitochondrial membrane potential (MMP, ΔΨ

Topics: Aminoglycosides; Animals; Cell Death; Diterpenes; Drug Delivery Systems; Ear, Inner; Gentamicins; Hair Cells, Auditory; Hearing Loss; Lactic Acid; Lateral Line System; Membrane Potential, Mitochondrial; Mitochondria; Nanoparticles; Oligopeptides; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Protective Agents; Zebrafish