Local treatment of the inner ear: A study of three different polymers aimed for middle ear administration

Abstract

Conclusion: A formulation based on sodium hyaluronate (NaHYA) was the most promising candidate vehicle for intra-tympanic drug administration regarding conductive hearing loss, inflammatory reactions, and elimination. Objectives: Recent advances in inner ear research support the idea of using the middle ear cavity for drug administration to target the inner ear. This paper presents rheological and safety assessments of three candidate polymer formulations for intra-tympanic drug administration. Method: The formulations were based on sodium carboxymethyl cellulose (NaCMC), sodium hyaluronate (NaHYA), and poloxamer 407 (POL). Rheological studies were performed with a controlled rate instrument of the couette type. Safety studies were performed in guinea pigs subjected to an intra-tympanic injection of the formulations. Hearing function was explored with ABR before and 1, 2, and 3 weeks after the injection. Elimination of the formulations marked with coal was explored with an endoscopic digital camera 1, 2, and 3 weeks after injection. Middle and inner ear morphology was examined with light microscopy 6 days after injection. Results: The results speak in favor of NaHYA, since it did not cause prolonged hearing threshold elevations. The results of the elimination and morphological investigations support the conclusion of NaHYA being the most promising candidate for intra-tympanic administration.

Keywords:

• ABR
• carboxymethyl cellulose
• guinea pig
• hyaluronan
• intra-tympanic
• morphology
• poloxamer 407
• polymer
• targeted drug delivery
• toxicity

Acknowledgments

The authors acknowledge Staffan Eksborg for the statistical analyses and AFA, the Acta Oto-Laryngologica Foundation, and Rosa and Emanuel Nachmansson’s Foundation for their generous financial support for the conduct of the research and preparation of the article. The foundations had no involvement in the study design, in the collection, analysis, and interpretation of data, in the writing of the report nor in the decision to submit the paper for publication.

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