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Int J Pharm. 2016 Apr 30;503(1-2):229-37. doi: 10.1016/j.ijpharm.2016.02.048. Epub 2016 Mar 10.

Inner ear delivery of dexamethasone using injectable silk-polyethylene glycol (PEG) hydrogel.

Author information

1
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.
2
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.
3
National Engineering Laboratory for Modern Silk, Soochow University, Suzhou 215123, China.
4
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@sh163.net.
5
National Engineering Laboratory for Modern Silk, Soochow University, Suzhou 215123, China. Electronic address: wangxiaoqin@suda.edu.cn.
6
Department of Otology and Laryngology, Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02115, USA.

Abstract

Minimally invasive delivery and sustained release of therapeutics to the inner ear are of importance to the medical treatment of inner ear disease. In this study, the injectable silk fibroin-polyethylene glycol (Silk-PEG) hydrogel was investigated as a drug delivery carrier to deliver poorly soluble micronized dexamethasone (mDEX) to the inner ear of guinea pigs. Encapsulation of mDEX with a loading up to 5% (w/v) did not significantly change the silk gelation time, and mDEX were evenly distributed in the PEG-Silk hydrogel as visualized by SEM. The loading of mDEX in Silk-PEG hydrogel largely influenced in vitro drug release kinetics. The optimized Silk-PEG-mDEX hydrogel (2.5% w/v loading, in situ-forming, 10 μl) was administered directly onto the round window membrane of guinea pigs. The DEX concentration in perilymph maintained above 100 ng/ml for at least 10 days for the Silk-PEG formulation while less than 12h for the control sample of free mDEX. Minimal systemic exposure was achieved with low DEX concentrations (<0.2 μg/ml) in cerebrospinal fluid (CSF) and plasma in the first 2h after the local application of the Silk-PEG-mDEX hydrogel. A transient hearing threshold shift was found but then resolved after 14 days as revealed by auditory brainstem response (ABR), showing minimal inflammatory responses on the round window membrane and scala taympani. The Silk-PEG hydrogel completely degraded in 21 days. Thus, the injectable PEG-Silk hydrogel is an effective and safe vehicle for inner ear delivery and sustained release of glucocorticoid.

KEYWORDS:

Dexamethasone; Drug delivery; Hydrogel; Inner ear; Silk fibroin

PMID:
26972377
DOI:
10.1016/j.ijpharm.2016.02.048
[Indexed for MEDLINE]

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