Preliminary Evaluation of an Injectable Therapeutic for Cisplatin Ototoxicity Using Neuronal SH-SY5Y Cells

Area of Science:

• Neuroscience
• Biomedical Engineering
• Pharmacology

Background:

• Cisplatin chemotherapy can cause ototoxicity by damaging inner ear neurons.
• There is a need for models to screen otoprotective drugs and develop localized treatments.
• Microparticle drug delivery offers sustained therapeutic release for managing side effects.

Purpose of the Study:

• To screen potential therapeutics for cisplatin-induced ototoxicity using a neuronal cell model.
• To develop and characterize N-acetylcysteine (NAC)-loaded microparticles for sustained drug delivery.
• To evaluate the potential of NAC and microparticle formulations in preventing cisplatin ototoxicity.

Main Methods:

• SH-SY5y human neuroblastoma cells modeled spiral ganglion neurons and were treated with cisplatin and potential therapeutics.
• Cell viability was assessed using CCK-8 assays after treatment with cisplatin and N-acetylcysteine (NAC).
• NAC was encapsulated into poly(lactic-co-glycolic acid) (PLGA) microparticles with varying ratios, and elution profiles were analyzed.

Main Results:

• N-acetylcysteine (NAC) significantly improved cell viability when administered before cisplatin exposure.
• The 75:25 lactide-glycolide (L:G) ratio microparticles released more NAC compared to 50:50 L:G microparticles.
• Elution studies confirmed detectable NAC release from microparticles for up to 6 days.

Conclusions:

• N-acetylcysteine (NAC) demonstrates potential as a therapeutic agent against cisplatin ototoxicity in a neuronal cell model.
• PLGA microparticles successfully encapsulated NAC, providing sustained release, a promising strategy for otoprotection.
• This study presents a method for screening therapeutics and a framework for developing local drug-eluting treatments for cisplatin-induced ototoxicity.