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

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

doi:10.1016/j.ijporl.2016.03.002

Cited by 13 publications

(8 citation statements)

References 19 publications

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“…Our results demonstrate that the dual vehicle can significantly extend the residence time of the drug/vehicle in the middle ear. These results are in agreement with those seen for other IT vehicles, such as thermosensitive gels, liposomes, film forming agents, and superparamagnetic nanoparticles, which can extend drug residence time to several days to months [ 26 , 27 , 28 , 29 ].…”

Section: Discussionsupporting

confidence: 90%

Effect and Biocompatibility of a Cross-Linked Hyaluronic Acid and Polylactide-co-glycolide Microcapsule Vehicle in Intratympanic Drug Delivery for Treating Acute Acoustic Trauma

Cho

Kim

Hwang

et al. 2021

IJMS

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The treatment of acute hearing loss is clinically challenging due to the low efficacy of drug delivery into the inner ear. Local intratympanic administration of dexamethasone (D) and insulin-like growth factor 1 (IGF1) has been proposed for treatment, but they do not persist in the middle ear because they are typically delivered in fluid form. We developed a dual-vehicle drug delivery system consisting of cross-linked hyaluronic acid and polylactide-co-glycolide microcapsules. The effect and biocompatibility of the dual vehicle in delivering D and IGF1 were evaluated using an animal model of acute acoustic trauma. The dual vehicle persisted 10.9 times longer (8.7 days) in the middle ear compared with the control (standard-of-care vehicle, 0.8 days). The dual vehicle was able to sustain drug release over up to 1 to 2 months when indocyanine green was loaded as the drug. One-third of the animals experienced an inflammatory adverse reaction. However, it was transient with no sequelae, which was validated by micro CT findings, endoscopic examination, and histological assessment. Hearing restoration after acoustic trauma was satisfactory in both groups, which was further supported by comparable numbers of viable hair cells. Overall, the use of a dual vehicle for intratympanic D and IGF1 delivery may maximize the effect of drug delivery to the target organ because the residence time of the vehicle is prolonged.

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Section: Discussionsupporting

confidence: 90%

Effect and Biocompatibility of a Cross-Linked Hyaluronic Acid and Polylactide-co-glycolide Microcapsule Vehicle in Intratympanic Drug Delivery for Treating Acute Acoustic Trauma

Cho

Kim

Hwang

et al. 2021

IJMS

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“…Studies have demonstrated the efficiency of zebra-fish models in drug design 131 and middle ear infused, gelatine-based hydrogels appear promising as a means to deliver drugs to the cochlea. 132 A novel intra-tympanic polymer gel delivery system has been evaluated and tested as a strategy for antiviral drug delivery in a guinea pig model 133 and holds promise for providing antiviral therapy to the CMV-infected cochlea while sparing the patient the substantial toxicities associated with systemic delivery of antiviral agents.…”

Section: Discussionmentioning

confidence: 99%

Congenital hearing loss

Korver

Smith

Camp

et al. 2017

Nat Rev Dis Primers

422

310

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Congenital hearing loss (hearing loss present at birth) is one of the most prevalent chronic conditions in children. In the majority of developed countries, neonatal hearing-screening programmes enable early detection; early intervention will prevent delays in speech and language development and have long-lasting beneficial effects on social and emotional development and quality of life. A hearing loss diagnosis is usually followed by a search for an underlying aetiology. Congenital hearing loss might be attributed to environmental and prenatal factors, which prevail in low-income settings; congenital infections, particularly cytomegalovirus, are also a common risk factor for hearing loss. Genetic causes probably account for the majority of cases in developed countries; mutations can affect any component of the hearing pathway, in particular inner ear homeostasis (endolymph production and maintenance) and mechano-electrical transduction (conversion of a mechanical stimulus into electrochemical activity). Once the underlying cause of hearing loss is established, it might direct therapeutic decision-making and guide prevention and (genetic) counseling. Management options include specific antimicrobial therapies, surgical treatment of cranio-facial abnormalities and hearing aids. An improved understanding of the pathophysiology and molecular mechanisms underlying hearing loss and increased awareness of recent advances in genetic testing will promote the development of new treatment and screening strategies.

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“…27 A better understanding of the mechanisms for CMV-related SNHL could inform development of therapeutic options to prevent onset and further progression of SNHL in children with congenital CMV infection. 28 …”

Section: Discussionmentioning

confidence: 99%

Hearing Trajectory in Children with Congenital Cytomegalovirus Infection

Lanzieri

Chung

Leung

et al. 2018

Otolaryngol.--head neck surg.

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Objectives Compare hearing trajectories among children with symptomatic and asymptomatic congenital CMV infection through age 18 years and identify brain abnormalities associated with sensorineural hearing loss (SNHL) in asymptomatic case-patients. Study Design Longitudinal prospective cohort study. Setting Tertiary medical center. Subjects and Methods Ninety-six (4 symptomatic and 92 asymptomatic) case-patients identified through hospital-based newborn CMV screening during 1982–1992 and 72 symptomatic case-patients identified through referrals during 1993–2005. We used growth curve modeling to analyze hearing thresholds (0.5–8 kHz) by ear with increasing age and Cox regression to determine abnormal findings on head computed tomography (CT) scan associated with SNHL (hearing threshold ≥25 dB in any audiometric frequency) among asymptomatic case-patients. Results Fifty-six (74%) symptomatic and 20 (22%) asymptomatic case-patients had SNHL: congenital/early-onset SNHL was diagnosed in 78 (51%) and 10 (5%) ears, respectively, and delayed-onset SNHL in 25 (17%) and 20 (11%) ears; 49 (32%) and 154 (84%) ears had normal hearing. In affected ears, all frequency-specific hearing thresholds worsened with age. Congenital/early-onset SNHL was significantly worse (severe-profound range [>70dB]) than delayed-onset SNHL (mild-moderate range [26–55db]). Frequency-specific hearing thresholds were significantly different between symptomatic and asymptomatic case-patients at 0.5–1 kHz but not at higher frequencies (2–8 kHz). Among asymptomatic case-patients, white matter lucency was significantly associated with SNHL by age 5 years (hazard ratio=4.4; 95% confidence interval: 1.3–15.6). Conclusion Congenital/early-onset SNHL frequently resulted in severe to profound loss in both symptomatic and asymptomatic case-patients. White matter lucency in asymptomatic case-patients was significantly associated with SNHL by age 5 years.

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

Cited by 13 publications

References 19 publications

Effect and Biocompatibility of a Cross-Linked Hyaluronic Acid and Polylactide-co-glycolide Microcapsule Vehicle in Intratympanic Drug Delivery for Treating Acute Acoustic Trauma

Effect and Biocompatibility of a Cross-Linked Hyaluronic Acid and Polylactide-co-glycolide Microcapsule Vehicle in Intratympanic Drug Delivery for Treating Acute Acoustic Trauma

Congenital hearing loss

Hearing Trajectory in Children with Congenital Cytomegalovirus Infection

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