Combination therapies using an intratympanic polymer gel delivery system in the guinea pig animal model: A safety study

Douglas Sidell, Jonette A. Ward, Angad Pordal, Carson Quimby, Michel Nassar, Daniel I. Choo

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Objectives: High dose antivirals have been shown to cause hearing loss when applied via the intratympanic route. The aim of this study was to determine if a combination therapy using dexamethasone (DXA) with either Cidofovir (CDV) or Ganciclovir (GCV), in solution or in PLGA-PEG-PLGA (PPP) hydrogel, is innocuous to the inner ear. Methods: Cytomegalovirus (CMV)-free guinea pigs were separated into four principal study groups and treated via intratympanic injection (IT) of CDV/DXA solution, CDV/DXA Hydrogel, GCV/DXA solution and GCV/DXA hydrogel. Hearing thresholds were evaluated with pretreatment ABR and post injection weekly ABRs for a total follow up of 28 days. Temporal bone tissue was harvested and stained with Hematoxylin and Eosin for histologic analysis. Results: ABR analysis revealed that GCV/DXA in solution and in hydrogel led to a mild hearing loss at days 7-21 but returned to baseline by day 28 When administered via PPP hydrogel, CDV/DXA demonstrated mild persistent hearing loss at 32 kHz at 28 days. An inflammatory response was identified in the cochlear specimen of the CDV/DXA/PPP hydrogel group, in concert with mild hearing loss, at days 21 and 28. Conclusion: Results of this study support the safe intratympanic use of higher concentrations of antivirals when combined with DXA, both in solution and when applied via PPP hydrogel.

Original languageEnglish (US)
Pages (from-to)132-136
Number of pages5
JournalInternational Journal of Pediatric Otorhinolaryngology
Volume84
DOIs
Publication statusPublished - May 1 2016

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Keywords

  • Antiviral
  • Cidofovir
  • Dexamethasone
  • Ganciclovir
  • Hydrogel
  • Intratympanic

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Pediatrics, Perinatology, and Child Health

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