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Permeation of polyethylene glycols across the tympanic membrane.

ABSTRACT: Localized and non-invasive delivery of therapeutics across barriers in the body is challenging. Examples include the flux of drugs across the tympanic membrane (TM) for the treatment of middle ear infections, and across the round window to treat inner ear disease. With the emergence of macromolecular therapies, the question arises as to whether such delivery can be achieved with macromolecules. Here, we have used polyethylene glycols (PEGs) in solutions to investigate macromolecular permeation across the TM in the chinchilla ex vivo. As the molecular weight of PEG increased, flux across the TM decreased, with an exponential relationship between the apparent diffusion coefficient and the molecular weight of the polymers. PEG flux was further decreased if it was released from a poloxamer 407 hydrogel, and lessened with increasing hydrogel concentration. Our results provide a framework for understanding the permeation of macromolecules noninvasively across barriers.

SUBMITTER: Zhang W

PROVIDER: S-EPMC8601659 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceTympanic membrane retraction (TMR) is a relatively common otological finding. However, no consensus on its management exists. We are looking especially for a treatment strategy in the military population who are unable to attend frequent follow-up visits, and who experience relatively more barotrauma at great heights and depths and easily suffer from otitis externa from less hygienic circumstances.ObjectiveTo assess and summarize the available evidence for the effectiveness of surgical interventions and watchful waiting policy in patients with a tympanic membrane retraction.Evidence reviewThe protocol for this systematic review was published at Prospero (207859). PubMed, Embase, and the Cochrane Database of Systematic Reviews were systematically searched from inception up to September 2020 for published and unpublished studies. We included randomized trials and observational studies that investigated surgical interventions (tympanoplasty, ventilation tube insertion) and wait-and-see policy. The primary outcomes of this study were clinical remission of the tympanic membrane retraction, tympanic membrane perforations and cholesteatoma development.FindingsIn total, 27 studies were included, consisting of 1566 patients with TMRs. We included data from 2 randomized controlled trials (76 patients) and 25 observational studies (1490 patients). Seven studies (329 patients) investigated excision of the TMR with and without ventilation tube placement, 3 studies (207 patients) investigated the wait-and-see policy and 17 studies (1030 patients) investigated tympanoplasty for the treatment of TMRs.Conclusions and relevanceThis study provides all the studies that have been published on the surgical management and wait-and-policy for tympanic membrane retractions. No high level of evidence comparative studies has been performed. The evidence for the management of tympanic membrane retractions is heterogenous and depends on many factors such as the patient population, location and severity of the TMR and presence of other ear pathologies (e.g., perforation, risk of cholesteatoma and serous otitis media).

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Permeation of polyethylene glycols across the tympanic membrane.

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