Novel Atorvastatin-eluting Microparticles Provide Neuroprotection from Cisplatin Ototoxicity

Introduction: Cisplatin, a commonly used chemotherapeutic agent, results in irreversible bilateral high-frequency sensorineural hearing loss and tinnitus in up to 60% and 40% of patients, respectively; oral atorvastatin has been shown to reduce the incidence and severity of this hearing loss in patients undergoing cisplatin chemotherapy. By encapsulating atorvastatin into microparticles and placing them within a thermosensitive hydrogel, we created a novel local therapeutic that releases bioactive concentrations of atorvastatin in a cell culture model of cisplatin neurotoxicity.

Methods: From February to May 2025 Rat Schwann Cell (RSC96) cultures were pre-treated with varying concentrations of resuspended atorvastatin and eluted atorvastatin before treatment with cisplatin. Cell viability was assessed and the resulting absorbances were analyzed via two-way ANOVA. Eluted atorvastatin was quantified via High Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS).

Results: We found resuspended atorvastatin improved cell viability after cisplatin exposure at 10 – 1,000 ng/ml (p <.01). After encapsulating atorvastatin into microparticles, we found retained bioactivity at 0.0025-1.25 mg/ml when released from water and 0.0025-0.25 mg/ml when released from a thermosensitive hydrogel (p <.01). Using HPLC-MS, we found that our microparticles continued to release 560 ng (4.98% relative standard deviation) in water 7 weeks after administration.

Conclusions: We identified a therapeutic range of resuspended atorvastatin and encapsulated atorvastatin into microparticles with retained bioactivity in our RSC96 cell culture model of cisplatin neurotoxicity. Our microparticles continued to release a therapeutic concentration of atorvastatin at 7 weeks. Further efforts are ongoing to further quantify atorvastatin released from our microparticles using HPLC-MS analysis to determine the full duration of drug release from a single administration.