Dexamethasone loaded nanoparticles exert protective effects against Cisplatin-induced hearing loss by systemic administration
Dexamethasone loaded nanoparticles exert protective effects against Cisplatin-induced hearing loss by systemic administration
复制标题
负载地塞米松的纳米颗粒通过全身给药对顺铂引起的听力损失发挥保护作用
DOI：
10.1016/j.neulet.2016.03.012
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发表时间：
2016-04-21
影响因子：
2.5
通讯作者：
Wu, Hao
中科院分区：
文献类型：
--
作者：
Sun, Changling;Wang, Xueling;Wu, Hao
耳毒性是顺铂化疗最重要的不良反应之一。作为急性感音神经性听力损失的常用治疗方法，已发表的研究表明，全身给予类固醇对顺铂诱导的听力损失（CIHL）无效。本研究旨在评价地塞米松（DEX）聚乙二醇-聚乳酸（PEG-PLA）纳米粒（DEX-NPs）对顺铂诱导的听力损失的潜在保护作用。如前所述，使用乳化和蒸发技术将DEX制备成PEG-PLA纳米颗粒。在顺铂给药前1小时，将DEX或DEX-NP腹膜内给药至豚鼠。在顺铂注射前1天和注射后3天，在4个频率（4，8，16和24 kHz）下测量听觉脑干反应（ABR）阈值偏移。通过耳蜗形态学观察评价顺铂对内耳的损伤。顺铂治疗前1小时单剂量的DEX-NP导致耳蜗的功能和结构特性的显著保留，这相当于多剂量（3天）DEX注射的效果。相反，单次注射DEX没有观察到显著的保护作用。耳蜗组织学检查结果与功能测定结果一致。总之，单剂量DEX-NP在组织学和功能水平上在全身给药后显著减弱了豚鼠中的顺铂耳毒性，表明这些纳米颗粒用于增强DEX在急性感音神经性听力损失中的递送的潜在治疗益处。(C)2016爱思唯尔爱尔兰有限公司版权所有。
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 polyethyleneglycolcoated 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 1 h before cisplatin administration. Auditory brainstem response (ABR) threshold shifts were measured at four frequencies (4, 8, 16, and 24 kHz) 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 1 h 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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.