Studies on slow release antibiotic middle ear pellets
Otitis Media with Effusion (OME) is the commonest cause of paediatric hearing impairment globally. Antibiotic laden pellets placed in the middle ear (ME) present a potential novel treatment strategy for OME disrupting the middle ear biofilm and avoiding systemic side effects. In vitro studies of Sta...
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| Format: | Thesis (University of Nottingham only) |
| Language: | English |
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2019
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| Online Access: | https://eprints.nottingham.ac.uk/56413/ |
| _version_ | 1848799326318362624 |
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| author | Hoskison, Emma |
| author_facet | Hoskison, Emma |
| author_sort | Hoskison, Emma |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Otitis Media with Effusion (OME) is the commonest cause of paediatric hearing impairment globally. Antibiotic laden pellets placed in the middle ear (ME) present a potential novel treatment strategy for OME disrupting the middle ear biofilm and avoiding systemic side effects. In vitro studies of Staphylococcus Aureus biofilm eradication with pellets laden with rifampicin and clindamycin demonstrate a future potential OME treatment and this study aims to establish the safety of these pellets in vivo.
Rifampicin (1.8mM) and clindamycin (35.3mM) loaded pellets made of poly lactic-co-glycolic acid and pluronic were surgically placed in guinea pig middle ears.
Auditory Brainstem Responses (ABRs) thresholds between 8-30 kHz were tested over 16 weeks alongside controls to assess for ototoxicity; amplitudes and latencies studied to assess for neurotoxicity. At one week post insertion of antibiotic laden pellets, marked ABR threshold elevation (15-40 dB) was observed and persisted (25-40 dB) at week 16 without accompanying changes in ABR wave amplitudes and latencies. This pattern therefore does not support a neurotoxic mechanism.
Representative cytocochleograms and immunofluorescence of the cochleas did not exhibit any appreciable frank outer or inner hair cell loss from the guinea pigs loaded with rifampicin and clindamycin pellets. This suggests that the pellets are not causing threshold elevation via an ototoxic mechanism.
ME histology revealed pellet remnants causing a moderate inflammatory response persisting at 16 weeks. With evidence of chronic inflammation in the middle ear, an associated ME effusion which has been undetected experimentally may underlie the ABR threshold elevation seen with rifampicin and clindamycin laden pellets. Confined to the middle ear, this may also explain the lack of IHC and OHC damage.
As a delivery vehicle to the ME, PLGA and Pluronic pellets have potential, but further studies are required on their antibiotic carriage to the middle ear before in vivo use. |
| first_indexed | 2025-11-14T20:33:53Z |
| format | Thesis (University of Nottingham only) |
| id | nottingham-56413 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T20:33:53Z |
| publishDate | 2019 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-564132025-02-28T14:27:52Z https://eprints.nottingham.ac.uk/56413/ Studies on slow release antibiotic middle ear pellets Hoskison, Emma Otitis Media with Effusion (OME) is the commonest cause of paediatric hearing impairment globally. Antibiotic laden pellets placed in the middle ear (ME) present a potential novel treatment strategy for OME disrupting the middle ear biofilm and avoiding systemic side effects. In vitro studies of Staphylococcus Aureus biofilm eradication with pellets laden with rifampicin and clindamycin demonstrate a future potential OME treatment and this study aims to establish the safety of these pellets in vivo. Rifampicin (1.8mM) and clindamycin (35.3mM) loaded pellets made of poly lactic-co-glycolic acid and pluronic were surgically placed in guinea pig middle ears. Auditory Brainstem Responses (ABRs) thresholds between 8-30 kHz were tested over 16 weeks alongside controls to assess for ototoxicity; amplitudes and latencies studied to assess for neurotoxicity. At one week post insertion of antibiotic laden pellets, marked ABR threshold elevation (15-40 dB) was observed and persisted (25-40 dB) at week 16 without accompanying changes in ABR wave amplitudes and latencies. This pattern therefore does not support a neurotoxic mechanism. Representative cytocochleograms and immunofluorescence of the cochleas did not exhibit any appreciable frank outer or inner hair cell loss from the guinea pigs loaded with rifampicin and clindamycin pellets. This suggests that the pellets are not causing threshold elevation via an ototoxic mechanism. ME histology revealed pellet remnants causing a moderate inflammatory response persisting at 16 weeks. With evidence of chronic inflammation in the middle ear, an associated ME effusion which has been undetected experimentally may underlie the ABR threshold elevation seen with rifampicin and clindamycin laden pellets. Confined to the middle ear, this may also explain the lack of IHC and OHC damage. As a delivery vehicle to the ME, PLGA and Pluronic pellets have potential, but further studies are required on their antibiotic carriage to the middle ear before in vivo use. 2019-07-19 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/56413/1/Thesis%20post%20corrections%20clean.pdf Hoskison, Emma (2019) Studies on slow release antibiotic middle ear pellets. PhD thesis, University of Nottingham. Antibiotic loaded pellets |
| spellingShingle | Antibiotic loaded pellets Hoskison, Emma Studies on slow release antibiotic middle ear pellets |
| title | Studies on slow release antibiotic middle ear pellets |
| title_full | Studies on slow release antibiotic middle ear pellets |
| title_fullStr | Studies on slow release antibiotic middle ear pellets |
| title_full_unstemmed | Studies on slow release antibiotic middle ear pellets |
| title_short | Studies on slow release antibiotic middle ear pellets |
| title_sort | studies on slow release antibiotic middle ear pellets |
| topic | Antibiotic loaded pellets |
| url | https://eprints.nottingham.ac.uk/56413/ |