Dataset Information

Comparison of the Pathway to the Inner Ear Between Postauricular and Intramuscular Injection of Dexamethasone in Guinea Pigs.

ABSTRACT:

Background

Postauricular injection as a local therapy has been confirmed to be effective for inner ear diseases. However, the mechanism for the drugs entering the inner ears remains unknown. This study aims to compare the distribution of dexamethasone by intramuscular injection with that by postauricular injection, and explore the pathway of the drugs entering the inner ears.

Methods

An in vivo optical imaging system was used to conduct a time course observation to compare the distribution of dexamethasone by intramuscular injection with that by postauricular injection in male guinea pigs. The drug availability in the tympanic mucosa, tympanum, endolymphatic sac, and cochlea was observed by a confocal laser scanning microscope.

Results

The local fluorescent intensity by postauricular injection was significantly higher in the inner ears, and lower in partial peripheral organs, than that by the intramuscular injection. The drug metabolism by postauricular injection exhibited an obviously sustained release effect in the inner ears. Drugs by postauricular injection might enter the endolymphatic sac through the posterior auricular artery and occipital artery, as well as the connections of the mastoid emissary vein, sigmoid sinus and endolymphatic sac.

Conclusion

More drugs concentrated in the inner ear for longer therapeutic time and less systemic delivery implied more effective and less risk of side effects through postauricular injection than intramuscular injection safer for the treatment of inner ear diseases.

SUBMITTER: Chen A

PROVIDER: S-EPMC8930822 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Comparison of the Pathway to the Inner Ear Between Postauricular and Intramuscular Injection of Dexamethasone in Guinea Pigs.

Chen Aiping A Liu Wenwen W Xu Lei L Hou Zhiqiang Z Fan Zhaomin Z Wang Haibo H Wang Mingming M

Frontiers in neurology 20220304

<h4>Background</h4>Postauricular injection as a local therapy has been confirmed to be effective for inner ear diseases. However, the mechanism for the drugs entering the inner ears remains unknown. This study aims to compare the distribution of dexamethasone by intramuscular injection with that by postauricular injection, and explore the pathway of the drugs entering the inner ears.<h4>Methods</h4>An <i>in vivo</i> optical imaging system was used to conduct a time course observation to compare ...[more]

PMID: 35309581

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Project description:Introduction: One major obstacle in validating drugs for the treatment or prevention of hearing loss is the limited data available on the distribution and concentration of drugs in the human inner ear. Although small animal models offer some insights into inner ear pharmacokinetics, their smaller organ size and different barrier (round window membrane) permeabilities compared to humans can complicate study interpretation. Therefore, developing a reliable large animal model for inner ear drug delivery is crucial. The inner and middle ear anatomy of domestic pigs closely resembles that of humans, making them promising candidates for studying inner ear pharmacokinetics. However, unlike humans, the anatomical orientation and tortuosity of the porcine external ear canal frustrates local drug delivery to the inner ear. Methods: In this study, we developed a surgical technique to access the tympanic membrane of pigs. To assess hearing pre- and post-surgery, auditory brainstem responses to click and pure tones were measured. Additionally, we performed 3D segmentation of the porcine inner ear images and used this data to simulate the diffusion of dexamethasone within the inner ear through fluid simulation software (FluidSim). Results: We have successfully delivered dexamethasone and dexamethasone sodium phosphate to the porcine inner ear via the intratympanic injection. The recorded auditory brainstem measurements revealed no adverse effects on hearing thresholds attributable to the surgery. We have also simulated the diffusion rates for dexamethasone and dexamethasone sodium phosphate into the porcine inner ear and confirmed the accuracy of the simulations using in-vivo data. Discussion: We have developed and characterized a method for conducting pharmacokinetic studies of the inner ear using pigs. This animal model closely mirrors the size of the human cochlea and the thickness of its barriers. The diffusion time and drug concentrations we reported align closely with the limited data available from human studies. Therefore, we have demonstrated the potential of using pigs as a large animal model for studying inner ear pharmacokinetics.

Dataset Information

Comparison of the Pathway to the Inner Ear Between Postauricular and Intramuscular Injection of Dexamethasone in Guinea Pigs.

Background

Methods

Results

Conclusion

Publications

Comparison of the Pathway to the Inner Ear Between Postauricular and Intramuscular Injection of Dexamethasone in Guinea Pigs.

Similar Datasets

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