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Local treatment of the inner ear: A study of three different polymers aimed for middle ear administration
Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
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2015 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 135, no 10, 985-994 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2015. Vol. 135, no 10, 985-994 p.
Keyword [en]
ABR, carboxymethyl cellulose, guinea pig, hyaluronan, intra-tympanic, morphology, poloxamer 407, polymer, targeted drug delivery, toxicity
National Category
Otorhinolaryngology
Identifiers
URN: urn:nbn:se:uu:diva-265635DOI: 10.3109/00016489.2015.1058534ISI: 000361294200004OAI: oai:DiVA.org:uu-265635DiVA: diva2:866927
Funder
AFA Insurance
Available from: 2015-11-04 Created: 2015-11-02 Last updated: 2017-12-01Bibliographically approved

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Pierre, Pernilla VidehultBramer, TobiasLaurell, Göran

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Otolaryngology and Head and Neck SurgeryDepartment of Pharmacy
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