A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration.
A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration.
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单剂量封装在聚乙二醇涂层聚乳酸纳米颗粒中的地塞米松可减轻圆窗膜给药后顺铂引起的听力损失
DOI：
10.2147/ijn.s77912
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发表时间：
2015
影响因子：
8
通讯作者：
Wu H
中科院分区：
文献类型：
--
作者：
Sun C;Wang X;Zheng Z;Chen D;Wang X;Shi F;Yu D;Wu H
研究聚乙二醇-聚乳酸（PEG-PLA）隐形纳米粒载地塞米松（DEX）的药物缓释性能和听力保护作用。如前所述，使用乳化和蒸发技术将DEX制成PEG-PLA纳米颗粒。载有DEX的PEG-PLA纳米颗粒（DEX-NPs）的流体动力学直径为130±4.78 nm，zeta电位为−26.13±3.28 mV。DEX从DEX-NP的体外释放在磷酸盐缓冲盐水（pH 7.4）中持续24天，在人工外淋巴液（pH 7.4）中持续5天，在大鼠血浆中持续1天。将香豆素6标记的NPs置于豚鼠的圆窗膜（RWM）上，在给药1小时后迅速穿透RWM并积累到Corti器官、血管纹和螺旋神经节细胞。通过单次给药将DEX-NPs局部应用于豚鼠的RWM，在48小时内持续释放DEX，这显著长于以相同剂量给药后12小时内清除的游离DEX。进一步的功能研究表明，局部给药的单剂量DEX-NP在顺铂损伤后有效地保存了豚鼠的外毛细胞，因此与游离DEX制剂的对照相比，在4kHz和8 kHz频率下显著减弱了听力损失。组织学分析表明，给予DEX-NP不会诱导局部炎症反应。因此，PEG-PLA纳米颗粒通过局部RWM扩散（给药）延长DEX的递送显著保护豚鼠的毛细胞和听觉功能免受顺铂毒性，如在组织学和功能水平上所确定的，表明在临床应用中的潜在治疗益处。
This study aimed to investigate the sustained drug release properties and hearing protection effect of polyethylene glycol-coated polylactic acid (PEG-PLA) stealth nanoparticles loaded with dexamethasone (DEX). DEX was fabricated into PEG-PLA nanoparticles using an emulsion and evaporation technique, as previously reported. The DEX-loaded PEG-PLA nanoparticles (DEX-NPs) had a hydrodynamic diameter of 130±4.78 nm, and a zeta potential of −26.13±3.28 mV. The in vitro release of DEX from DEX-NPs lasted 24 days in phosphate buffered saline (pH 7.4), 5 days in artificial perilymph (pH 7.4), and 1 day in rat plasma. Coumarin 6-labeled NPs placed onto the round window membrane (RWM) of guinea pigs penetrated RWM quickly and accumulated to the organs of Corti, stria vascularis, and spiral ganglion cells after 1 hour of administration. The DEX-NPs locally applied onto the RWM of guinea pigs by a single-dose administration continuously released DEX in 48 hours, which was significantly longer than the free DEX that was cleared out within 12 hours after administration at the same dose. Further functional studies showed that locally administrated single-dose DEX-NPs effectively preserved outer hair cells in guinea pigs after cisplatin insult and thus significantly attenuated hearing loss at 4 kHz and 8 kHz frequencies when compared to the control of free DEX formulation. Histological analyses indicated that the administration of DEX-NPs did not induce local inflammatory responses. Therefore, prolonged delivery of DEX by PEG-PLA nanoparticles through local RWM diffusion (administration) significantly protected the hair cells and auditory function in guinea pigs from cisplatin toxicity, as determined at both histological and functional levels, suggesting the potential therapeutic benefits in clinical applications.