title: Ultrasound-aided microbubbles facilitate the delivery of drugs to the inner ear via the round window membrane.
abstract: 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. In this study, we targeted the practical application of microbubbles (MBs) 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. We herein provide a basis for MB ultrasound-mediated techniques with therapeutic medication delivery to the inner ear for future application in humans.
authors: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
authors: Cheng-Ping
authors: CP
authors: Shih
authors: Hsin-Chien
authors: HC
authors: Chen
authors: Hang-Kang
authors: HK
authors: Chen
authors: Min-Chang
authors: MC
authors: Chiang
authors: Huey-Kang
authors: HK
authors: Sytwu
authors: Yi-Chun
authors: YC
authors: Lin
authors: Shiue-Li
authors: SL
authors: Li
authors: Yu-Fan
authors: YF
authors: Shih
authors: Ai-Ho
authors: AH
authors: Liao
authors: Chih-Hung
authors: CH
authors: Wang
mesh_terms: D000162:Acoustics; D000818:Animals; D001710:Biotin / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D007758:Ear, Inner / Q000378:metabolism*; D016057:Evoked Potentials, Auditory, Brain Stem; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000737:chemistry; D005839:Gentamicins / Q000008:administration & dosage / Q000737:chemistry; D006168:Guinea Pigs; D045423:Microbubbles; D014966:Xanthenes / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D005839:Gentamicins; D014966:Xanthenes; D001710:Biotin; C034657:Texas red; D016650:Fluorescein-5-isothiocyanate