Abstract

We present a topical drug delivery mechanism through the ear canal to the middle and inner ear using liposomal nanoparticles without disrupting the integrity of the tympanic membrane. The current delivery method provides a non-invasive,and safer alternative to trans-tympanic membrane injections, ear tubes followed by ear drops administration and systemic drug formulations. We investigate the capability of liposomal NPs, particularly transfersomes (TLipo), used as drug delivery vesicles to penetrate the tympanic membrane (TM) and round window membrane (RWM) with high affinity, specificity, and retention time. The TLipo is applied to the ear canal and found to pass through tympanic membrane quickly in 3 hours post drug administration. They are identified in the middle ear cavity 6 hours and in the inner ear 24 hours after drug administration. We performed cytotoxicity in vitro and ototoxicity in vivo studies. Cell viability shows no significant difference between the applied TLipo concentration and control. Furthermore, auditory brainstem response (ABR) reveals no hearing loss in 1 week and 1 month post administration. Immunohistochemistry results demonstrates no evidence of hair cell loss in the cochlea at 1 month following TLipo administration. Together, the data suggested that TLipo can be used as a vehicle for topical drug delivery to the middle ear and inner ear.