Inner ear drug delivery system from the clinical point of view

Abstract

Conclusion: Three types of inner ear drug delivery systems (DDS) that were ready to be applied in clinics were developed. Objectives: To develop clinically applicable inner ear DDS for the treatment of inner ear disorders. Methods: Inner ear DDS using clinically applicable materials were developed and evaluated. Results: The systemic application of stealth-type nanoparticles encapsulating betamethasone provided superior therapeutic results for the treatment of noise-induced hearing loss compared with the systemic application of betamethasone in mice. Microparticles made of biodegradable polymer (poly (lactic/glycolic) acid, PLGA) encapsulating lidocaine were placed on the round window membrane of guinea pigs, and resulted in reasonable concentrations of lidocaine in the cochlea without serious adverse effects. The phase I/IIa clinical trial of the application of insulin-like growth factor-1 (IGF-1) in combination with gelatin hydrogel on the round window membrane was conducted, recruiting patients with acute sensorineural hearing loss after the failure of systemic application of steroids.

Keywords::

• Sensorineural hearing loss
• tinnitus
• biodegradable polymer
• gelatin hydrogel
• betamethasone
• insulin-like growth factor 1
• lidocaine

Acknowledgments

This study was supported by Grant-in-Aids for Researches from the Japanese Ministry of Health, Labour and Welfare and from the the Ministry of Education, Culture, Sports, Science and Technology. Stealth-type nanoparticles were kindly provided by Dr Tsutomu Ishihara (Research Institute for Drug Discovery, Graduate School of Medical Sciences, Kumamoto University) and Prof. Megumu Higaki (Jikei University School of Medicine). Microparticles encapsulating lidocaine and the IGF-1 releasing system using gelatin hydrogel were developed with the intensive support of Prof. Yasuhiko Tabata (Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University). The clinical trial was totally supported by Prof. Ken-ichi Inui (Department of Pharmacy, Kyoto University Hospital) and the Translational Research Center of Kyoto University Hospital.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.