Probucol-Bile Acid Based Nanoparticles Protect Auditory Cells from Oxidative Stress: An In Vitro Study

Abstract

Aim:

Excessive free radicals contribute to oxidative stress and mitochondrial dysfunction in sensorineural hearing loss (SNHL). The antioxidant probucol holds promise, but its limited bioavailability and inner ear barriers hinder effective SNHL treatment.

Methodology:

We addressed this by developing probucol-loaded nanoparticles with polymers and lithocholic acid and tested them on House Ear Institute-Organ of Corti cells.

Results:

Probucol-based nanoparticles effectively reduced oxidative stress-induced apoptosis, enhanced cellular viability, improved probucol uptake and promoted mitochondrial function. Additionally, they demonstrated the capacity to reduce reactive oxygen species through the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway.

Conclusion:

This innovative nanoparticle system holds the potential to prevent oxidative stress-related hearing impairment, providing an effective solution for SNHL.

Plain language summary

Hearing loss affects millions of people worldwide, and its prevalence is expected to double by 2050. Current treatments have limitations, pushing researchers to explore new options. Oxidative stress is a key player in hearing loss and is known to damage inner ear hair cells. While antioxidants, known for their protective effects, hold promise, delivering them effectively to the inner ear is challenging. Scientists have been testing nanoparticles loaded with the antioxidant probucol to fight hearing loss. In this study, these particles protected inner ear cells in cell studies, offering potential hope for preventing hearing problems. This research is a significant step toward finding better treatments for hearing loss.

Graphical abstract

Keywords::

• bile acid
• hearing impairment
• nanoparticles
• oxidative stress
• probucol

Author contributions

Conceptualization, H Al-Salami, M Mikov, A Mooranian and A Wise; Data curation S Raj Wagle, CM Ionescu, B Kovacevic, M Jones and T Foster; funding acquisition, H Al-Salami, M Mikov and A Mooranian; investigation, all authors; methodology, S. Raj Wagle, CM Ionescu, B Kovacevic, M Jones, T Foster; project administration, H Al-Salami, M Mikov, A Mooranian and A Wise; resources, H Al-Salami, M Mikov, A Mooranian and A Wise; supervision, H Al-Salami, M Mikov, A Mooranian and A Wise; validation, S Raj Wagle, CM Ionescu, B Kovacevic, M Jones, T Foster and; visualization, S Raj Wagle, CM Ionescu, B Kovacevic, M Jones, T Foster; writing-original draft, S Raj Wagle; writing-review & editing, all authors. All authors have read and agreed to the published version of the manuscript.

Acknowledgments

The authors acknowledge the Australian Research Training Program Scholarship for their support, Mr. Michael Nesbit from the Confocal Curtin Health Innovation Research Institute Microscopy for assistance with Andor Dragonfly supported by the Australian Research Council – LIEF LE200100122. The authors are very grateful to YJ Seo (Yonsei University Wonju College of Medicine) and F Kalinec (UCLA) for the auditory cells.

Financial disclosure

Curtin Faculty ORS-WAHAI Consortium, the Australian National Health and Medical Research (APP9000597) partially support this work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

H Al-Salamiis currently receiving funding from Austin Biotec Pty, Ltd and Glanis PTY Ltd. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Edboard disclosure

H Al Salami is a member of the Therapeutic Delivery Editorial Board. They were not involved in any editorial decisions related to the publication of this article, and all author details were blinded to the article’s peer reviewers as per the journal’s double-blind peer review policy.

Data availability

All data is available upon request to the corresponding author.

Additional information

Funding

Curtin Faculty ORS-WAHAI Consortium, the Australian National Health and Medical Research (APP9000597) partially support this work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.