Is postauricular injection a systemic or a topical route for inner ear drug delivery?

The challenges associated with the blood-labyrinth barrier and unwanted systemic adverse effects severely impede the development of systemic drug administration for inner ear therapy. Previous studies have demonstrated that postauricular injection might be an alternative route for the systemic administration for inner ear therapy because it is minimally invasive and can achieve a high drug concentration in the inner ear. However, the in vivo effects remain unclear. This study aimed to compare differences in cisplatin-induced ototoxicity and systemic adverse effects between postauricular and systemic administration. Here, we compared the differences in hair cell loss, body weight change, and renal dysfunction (indicated by serum levels of blood urea nitrogen and creatinine) between these two routes of administration. The results showed that although postauricular injection of cisplatin might induce greater hair cell damage in the ipsilateral cochleae than that after intraperitoneal injection, significant hair cell damage in the contralateral cochleae as well as systemic adverse effects were also observed. Our results indicated that: (1) topical administration effects might occur in the ipsilateral inner ear following postauricular injection, and (2) systemic circulation might also be an underestimated route of drug delivery to the inner ear following postauricular injection. Overall, postauricular injection is a hybrid administration route, which simultaneously shares the features of topical and systemic administration for inner ear drug delivery.