{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:27:35Z","timestamp":1768508855283,"version":"3.49.0"},"posted":{"date-parts":[[2023,11,2]]},"group-title":"Bioengineering","reference-count":21,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Cisplatin is known to cause inner ear dysfunction. There is growing evidence that cisplatin-induced demyelination of spiral or Scarpa\u2019s ganglion neurons may play an additional role in drug-induced ototoxicity alongside afferent neuron injury. As Schwann cells produce myelin, there may be an opportunity to reduce ototoxic inner ear damage by promoting Schwann cell viability. This work describes a cellular model of cisplatin-induced Schwann cell injury and investigates the ability of the antioxidant N-acetylcysteine to promote Schwann cell viability. A local delivery system of drug-eluting microparticles was then fabricated, characterized, and investigated for bioactivity.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    RSC96 rat Schwann cells were dosed with varying concentrations of cisplatin to obtain a dose curve and identify the lethal concentration of 50% of the cells (LC\n                    <jats:sub>50<\/jats:sub>\n                    ). In subsequent experiments, RSC96 cells were co-treated with cisplatin and both resuspended or eluted N-acetylcysteine. Cell viability was assessed with the CCK8 assay.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    The LC\n                    <jats:sub>50<\/jats:sub>\n                    dose of cisplatin was determined to be 3.76 \u03bcM (p=2.2 \u00d7 10\n                    <jats:sup>\u221216<\/jats:sup>\n                    ). When co-dosed with cisplatin and therapeutic concentration of resuspended or eluted N-acetylcysteine, Schwann cells had an increased viability compared to cells dosed with cisplatin alone.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>RSC96 Schwann cell injury following cisplatin insult is characterized in this in vitro model. Cisplatin caused injury at physiologic concentrations and N-acetylcysteine improved cell viability and mitigated this injury. N-acetylcysteine was packaged into microparticles and eluted N-acetylcysteine retained its ability to increase cell viability, thus demonstrating promise as a therapeutic to offset cisplatin-induced ototoxicity.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Lay Summary<\/jats:title>\n                  <jats:p>Cisplatin is a chemotherapeutic agent known to cause balance and hearing problems through damage to the inner ear. This project explored cisplatin injury in a Schwann cell culture model and packaged an antioxidant into microparticles suitable for future drug delivery applications.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.10.31.564430","type":"posted-content","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T03:44:30Z","timestamp":1698983070000},"source":"Crossref","is-referenced-by-count":2,"title":["N-acetylcysteine Microparticles Reduce Cisplatin-induced RSC96 Schwann Cell Toxicity"],"prefix":"10.64898","author":[{"given":"Katherine","family":"Kedeshian","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry","family":"Hoffman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley","family":"Kita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023110703150749000_2023.10.31.564430v1.1","doi-asserted-by":"publisher","DOI":"10.3390\/toxics3030268"},{"key":"2023110703150749000_2023.10.31.564430v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2015.06.012"},{"key":"2023110703150749000_2023.10.31.564430v1.3","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.219.177"},{"key":"2023110703150749000_2023.10.31.564430v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2005.08.068"},{"key":"2023110703150749000_2023.10.31.564430v1.5","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200101220-00035"},{"key":"2023110703150749000_2023.10.31.564430v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14487"},{"key":"2023110703150749000_2023.10.31.564430v1.7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1008499"},{"key":"2023110703150749000_2023.10.31.564430v1.8","doi-asserted-by":"crossref","unstructured":"Balakrishnan A , Belfiore L , Chu TH , et al. 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