| Summary: | 博士 === 國防醫學院 === 醫學科學研究所 === 104 === The round window membrane (RWM) acts as a barrier between the middle ear and cochlea and can serve as a crucial route for therapeutic medications entering the inner ear via middle ear applications. The approach in local delivery of drugs to inner ear includes intratympanic and intracochlear approach. The intratympanic approach has the advantage of no insult to inner ear structure and function in comparison of the intracochlear approach. Drug delivery via intratympanic approach depends on the permeation of round window membrane. Microbubbles (MBs) ultrasound is a promising technique that can promote drug delivery but was never applied to inner ear drug delivery. In this study, we targeted the practical application of MB ultrasound on increasing the RWM permeability for facilitating drug or medication delivery to the inner ear. Using biotin–fluorescein isothiocyanate conjugates (biotin–FITC) as delivery agents and guinea pig animal models, we showed that MB ultrasound exposure can improve the inner ear system use of biotin–FITC delivery via the RWM by approximately 3.5 to 38 times that of solely soaking biotin–FITC around the RWM for spontaneous diffusion. We also showed that there was significant enhancement of hair cell uptake of gentamicin in animals whose tympanic bullas were soaked with MB-mixed gentamicin–Texas Red or gentamicin and exposed to ultrasound. Furthermore, increased permeability of the RWM from acoustic cavitation of MBs could also be visualized immediately following ultrasound exposure by using Alexa Fluor 488-conjugated phalloidin as a tracer. Most importantly, such applications had no resulting damage to the integrity of the RWM or deterioration of the hearing thresholds assessed by auditory brainstem responses. The findings provide a basis for MB ultrasound-mediated techniques with therapeutic medication delivery to the inner ear for future application in humans. The next issues of experiments are to investigate the benefit of local drug delivery from MB ultrasound in the animal model of inner ear disease. The preliminary results in the ongoing experiments revealed this technique could promote dexamethasone and N-acetylcysteine delivering to inner ear and thus enhance the drug action to ameliorate noise-induced hearing loss.
|
|---|
