A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration

Changling Sun,1,3,* Xueling Wang,1,* Zhaozhu Zheng,2 Dongye Chen,1 Xiaoqin Wang,2 Fuxin Shi,1 Dehong Yu,1 Hao Wu11Department of Otolaryngology–Head and Neck Surgery, Xinhua Hospital, Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Translational M...

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Main Authors: Sun CL, Wang XL, Zheng ZZ, Chen DY, Wang XQ, Shi F, Yu DH, Wu H
Format: Article
Language:English
Published: Dove Medical Press 2015-05-01
Series:International Journal of Nanomedicine
Online Access:http://www.dovepress.com/a-single-dose-of-dexamethasone-encapsulated-in-polyethylene-glycol-coa-peer-reviewed-article-IJN
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spelling doaj-a29841bf71244739999ecbc4fd68edc92020-11-24T23:49:18ZengDove Medical PressInternational Journal of Nanomedicine1178-20132015-05-012015default3567357921739A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administrationSun CLWang XLZheng ZZChen DYWang XQShi FYu DHWu HChangling Sun,1,3,* Xueling Wang,1,* Zhaozhu Zheng,2 Dongye Chen,1 Xiaoqin Wang,2 Fuxin Shi,1 Dehong Yu,1 Hao Wu11Department of Otolaryngology–Head and Neck Surgery, Xinhua Hospital, Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, 2National Engineering Laboratory for Modern Silk, Soochow University, Suzhou, 3Department of Otolaryngology–Head and Neck Surgery, Affiliated Hospital of Jiangnan University, The Fourth People’s Hospital of Wuxi City, Wuxi, People’s Republic of China*These authors have contributed equally to this workAbstract: 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.Keywords: stealth nanoparticles, dexamethasone, single-dose administration, cisplatin-induced hearing losshttp://www.dovepress.com/a-single-dose-of-dexamethasone-encapsulated-in-polyethylene-glycol-coa-peer-reviewed-article-IJN
collection DOAJ
language English
format Article
sources DOAJ
author Sun CL
Wang XL
Zheng ZZ
Chen DY
Wang XQ
Shi F
Yu DH
Wu H
spellingShingle Sun CL
Wang XL
Zheng ZZ
Chen DY
Wang XQ
Shi F
Yu DH
Wu H
A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration
International Journal of Nanomedicine
author_facet Sun CL
Wang XL
Zheng ZZ
Chen DY
Wang XQ
Shi F
Yu DH
Wu H
author_sort Sun CL
title A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration
title_short A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration
title_full A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration
title_fullStr A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration
title_full_unstemmed A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration
title_sort single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration
publisher Dove Medical Press
series International Journal of Nanomedicine
issn 1178-2013
publishDate 2015-05-01
description Changling Sun,1,3,* Xueling Wang,1,* Zhaozhu Zheng,2 Dongye Chen,1 Xiaoqin Wang,2 Fuxin Shi,1 Dehong Yu,1 Hao Wu11Department of Otolaryngology–Head and Neck Surgery, Xinhua Hospital, Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, 2National Engineering Laboratory for Modern Silk, Soochow University, Suzhou, 3Department of Otolaryngology–Head and Neck Surgery, Affiliated Hospital of Jiangnan University, The Fourth People’s Hospital of Wuxi City, Wuxi, People’s Republic of China*These authors have contributed equally to this workAbstract: 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.Keywords: stealth nanoparticles, dexamethasone, single-dose administration, cisplatin-induced hearing loss
url http://www.dovepress.com/a-single-dose-of-dexamethasone-encapsulated-in-polyethylene-glycol-coa-peer-reviewed-article-IJN
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