The Application of Theranostic Microbubble Ultrasound System for the Minimally Invasive Surgery

Abstract

Sensorineural hearing loss and balance dysfunction are common symptoms of inner ear disorders. Therapeutic strategies may include medication, surgical intervention, sound amplification, or physical therapy. Methods for local delivery can include intratympanic or intracochlear approaches. Intracochlear drug delivery is achieved via a cochleostomy through the round window membrane (RWM) or directly through the otic capsule, and a variety of devices, including syringe, osmotic pumps, microinjector, and a reciprocating drug delivery system, have been employed. Although intracochlear application can achieve greater bioavailability of drugs entering the inner ear than the intratympanic approach, the former usually requires invasive surgical manipulation to interrupt the inner ear structure, and may increase the risk of deafness. Active intratympanic drug delivery was developed in an attempt to overcome the shortcomings of direct transtympanic injection. Potential utilization for such a topical application of medicine to the inner ear will be further explored in the future in view of its convenience in application, fewer side effects, and minimal invasiveness. Recently, ultrasound (US) combined with a contrast agent, microbubbles (MBs), has been used to target or control drug release to tissues and cells. MBs, which are small gas-filled microspheres that are used as contrast agents in diagnostic ultrasound-based imaging, are now being intensively investigated for ultrasound-mediated gene and drug delivery as cavitation nuclei. In this presentation, the feasibility of US combined with the most suitable particle size MBs to enhance the drug delivery by theranostic MBs-US system in inner ear was firstly demonstrated. The practical application of optimal MBs-US on increasing the RWM permeability for facilitating drug or medication delivery to the inner ear. Biotin–fluorescein isothiocyanate conjugates (biotin–FITC) are as delivery agents, and guinea pig animal models simulate the clinical case. Finally, the efficiency and feasibility of theranostic MBs-US system in clinical purpose will be assessed.