{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T05:15:40Z","timestamp":1765516540294,"version":"3.48.0"},"reference-count":39,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1K08DC019957-01"],"award-info":[{"award-number":["1K08DC019957-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005380","name":"American Neurotology Society","doi-asserted-by":"publisher","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}],"id":[{"id":"10.13039\/100005380","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicines"],"abstract":"<jats:p>Background\/Objectives: Though ototoxic, cisplatin is a mainstay of chemotherapy for a variety of cancers. One suggested mechanism of cisplatin ototoxicity involves damage to the spiral ganglion afferent neurons in the inner ear. There is a need for a high-throughput model to screen medications for efficacy against cisplatin and to develop a local therapeutic to mitigate cisplatin\u2019s debilitating side effects. Microparticles encapsulating a therapeutic medication are an injectable and tunable method of sustained drug delivery, and thus a promising treatment. Methods: SH-SY5y human neuroblastoma cells were used as a cell line model for the spiral ganglion neurons. The cells were dosed with cisplatin and four potential therapeutics (melatonin, metformin, cyclosporine, and N-acetylcysteine), with cell viability measured by CCK-8 assay. The most promising therapeutic, N-acetylcysteine (NAC), was then encapsulated into multiple poly(lactic-co-glycolic acid) (PLGA) microparticle subtypes of varied lactide\u2013glycolide (L:G) ratios and NAC amounts. The elution profile of each microparticle subtype was determined over two months. Results: Of the therapeutics screened, only cells dosed with 1 or 10 mM NAC prior to cisplatin injury demonstrated an improvement in cell viability (73.8%, p &lt; 1 \u00d7 10\u22128) when compared to cells dosed with cisplatin alone. The 75:25 L:G microparticles demonstrated an increase in the amount of NAC released compared to the 50:50 L:G microparticles. Conclusions: NAC is a potential therapeutic agent for cisplatin toxicity when tested in a neuronal cell line model. NAC was encapsulated into PLGA microparticles and eluted detectable concentrations of NAC for 6 days, which is a first step towards otoprotection for the weeks long duration of chemotherapy treatment. This work describes a method of screening potential therapeutics and a strategy to develop local drug eluting treatments to protect against cisplatin ototoxicity.<\/jats:p>","DOI":"10.3390\/medicines12040030","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T13:51:46Z","timestamp":1765288306000},"page":"30","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preliminary Evaluation of an Injectable Therapeutic for Cisplatin Ototoxicity Using Neuronal SH-SY5Y Cells"],"prefix":"10.3390","volume":"12","author":[{"given":"Michelle","family":"Hong","sequence":"first","affiliation":[{"name":"Los Angeles Department of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3088-7283","authenticated-orcid":false,"given":"Katherine","family":"Kedeshian","sequence":"additional","affiliation":[{"name":"Los Angeles Department of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Los Angeles Department of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2759-8271","authenticated-orcid":false,"given":"Ashley","family":"Kita","sequence":"additional","affiliation":[{"name":"Los Angeles Department of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1002\/ar.22578","article-title":"Cisplatin and aminoglycoside antibiotics: Hearing loss and its prevention","volume":"295","author":"Schacht","year":"2012","journal-title":"Anat. 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