Sustained delivery of lidocaine into the cochlea using poly lactic/glycolic acid microparticles.

OBJECTIVES/HYPOTHESIS: Lidocaine is a local anesthetic that is known to suppress tinnitus via systemic or local application; however, this effect has only limited duration. The current study aimed to establish a method for the sustained delivery of lidocaine into the cochlea using poly lactic/glycolic acid (PLGA) microparticles. STUDY DESIGN: Experimental study. METHODS: Lidocaine-loaded PLGA microparticles were produced and their in vitro-release profiles were examined. The lidocaine concentrations in the perilymph were measured at different time points following the application of the lidocaine-loaded PLGA microparticles to the round-window membranes of guinea pigs. The possible adverse effects of the local application of lidocaine-loaded PLGA microparticles were also examined. RESULTS: The in vitro analyses revealed that the microparticles were capable of the sustained delivery of lidocaine. The in vivo experiments demonstrated the sustained delivery of lidocaine into the cochlear fluid, and the maintenance of high lidocaine concentrations in the perilymph for up to 3 days after application. Nystagmus and inflammation in the middle ear mucosa were not detected after the local application of lidocaine-loaded PLGA microparticles, although temporary hearing loss was observed. CONCLUSIONS: Lidocaine-loaded PLGA microparticles were shown to be capable of the sustained delivery of lidocaine into the cochlea, suggesting that they could be used for the attenuation of peripheral tinnitus.

Stealth-nanoparticle strategy for enhancing the efficacy of steroids in mice with noise-induced hearing loss.

AIMS: This study aimed to investigate the efficacy of encapsulating steroids, which is a primary choice for the treatment of sensorineural hearing loss, in polyethylene glycol-coated polylactic acid nanoparticles for drug delivery to the cochlea. MATERIALS & METHODS: We prepared polyethylene glycol-coated polylactic acid nanoparticles encapsulating rhodamine or betamethasone phosphate (BP), and administered them systemically to CBA/N mice previously exposed to intense noise. We assessed nanoparticle distribution using rhodamine fluorescence, BP concentrations in tissues, nuclear translocation of glucocorticoid receptors and the function and histology of the mouse cochleae. RESULTS & CONCLUSION: Polyethylene glycol-coated polylactic acid nanoparticles delivered BP to cochleae over a sustained period, resulting in significant reductions in histological and functional damage to cochleae and indicating the potential therapeutic benefits of these nanoparticles for enhancing the delivery of BP in acute sensorineural hearing loss.