title: Dexamethasone loaded nanoparticles exert protective effects against Cisplatin-induced hearing loss by systemic administration.
abstract: Ototoxicity is one of the most important adverse effects of cisplatin chemotherapy. As a common treatment of acute sensorineural hearing loss, systemic administration of steroids was demonstrated ineffective against cisplatin-induced hearing loss (CIHL) in published studies. The current study aimed to evaluate the potential protective effect of dexamethasone (DEX) encapsulated in polyethyleneglycol-coated polylactic acid (PEG-PLA) nanoparticles (DEX-NPs) against cisplatin-induced hearing loss following systemic administration. DEX was fabricated into PEG-PLA nanoparticles using emulsion and evaporation technique as previously reported. DEX or DEX-NPs was administered intraperitoneally to guinea pigs 1h before cisplatin administration. Auditory brainstem response (ABR) threshold shifts were measured at four frequencies (4, 8, 16, and 24kHz) 1 day before and three days after cisplatin injection. Cochlear morphology was examined to evaluate inner ear injury induced by cisplatin exposure. A single dose of DEX-NPs 1h before cisplatin treatment resulted in a significant preservation of the functional and structural properties of the cochlea, which was equivalent to the effect of multidose (3 days) DEX injection. In contrast, no significant protective effect was observed by single dose injection of DEX. The results of histological examination of the cochleae were consistent with the functional measurements. In conclusion, a single dose DEX-NPs significantly attenuated cisplatin ototoxicity in guinea pigs after systemic administration at both histological and functional levels indicating the potential therapeutic benefits of these nanoparticles for enhancing the delivery of DEX in acute sensorineural hearing loss.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases, Shanghai 200092, China; Department of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Jiangnan University, The Fourth People's Hospital of Wuxi City, Wuxi 214062, China.
authors.forename: Changling
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases, Shanghai 200092, China.
authors.forename: Xueling
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases, Shanghai 200092, China.
authors.forename: Dongye
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases, Shanghai 200092, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases, Shanghai 200092, China. Electronic address: dehongyu@126.com.
authors.forename: Dehong
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases, Shanghai 200092, China. Electronic address: wuhao622@sina.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects* / Q000473:pathology; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016057:Evoked Potentials, Auditory, Brain Stem; D006168:Guinea Pigs; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D019344:Lactic Acid; D008297:Male; D053758:Nanoparticles; D011091:Polyesters; D011092:Polyethylene Glycols; D011108:Polymers; D013136:Spiral Ganglion / Q000187:drug effects / Q000473:pathology; D013316:Stria Vascularis / Q000187:drug effects / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); D003907:Dexamethasone; D002945:Cisplatin
keywords: Cisplatin-induced hearing loss; Dexamethasone; Stealth nanoparticles