Dexamethasone-loaded chitosan-based genipin-cross-linked hydrogel for prevention of cisplatin induced ototoxicity in Guinea pig model
Dexamethasone-loaded chitosan-based genipin-cross-linked hydrogel for prevention of cisplatin induced ototoxicity in Guinea pig model
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DOI：
10.1016/j.ijporl.2019.04.003
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发表时间：
2019-07-01
影响因子：
1.5
通讯作者：
Guneri, Enis Alpin
中科院分区：
文献类型：
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作者：
Aslier, Nesibe Gul Yuksel;Tagac, Aylin Altinisik;Guneri, Enis Alpin
目的：本研究的目的是探讨缓释形式的地塞米松 (dex) 负载壳聚糖基京尼平交联水凝胶 (CBGCH) 对顺铂 (CP) 诱导的听力损失豚鼠模型的保护作用。方法：通过鼓室内 (IT) 注射植入 CBGCH。腹膜内 (IP) 单剂量 14 mg/kg CP 产生耳毒性。将动物随机分为四组，每组 6 只豚鼠。第1组仅接收IP CP；第2组仅接受IT dex-loaded CBGCH注射。第3组和第4组在IP CP注射前24小时分别接受IP CP，加上IT非药物CBGCH和IT dex-loaded CBGCH。在治疗前获得失真产物耳声发射 (DPOAE) 和听觉脑干反应 (ABR) 测量，并在 3 天和 10 天后仅进行 ABR 测量。通过扫描电子显微镜 (SEM) 分析研究超微结构效应。结果：第 4 组在 4、8、12、16、32 kHz 频率下的 CP 后 ABR 阈值明显优于第 1 组和第 3 组 (p < 0.05)。第 1 组和第 4 组以及第 3 组和第 4 组之间的时间有效 ABR 阈值比较显示，第 4 组的 ABR 阈值显着较低 (p < 0.05)。 SEM 分析显示，第 4 组的内毛细胞和外毛细胞的静纤毛得到了保留，几乎与第 2 组相似，而第 1 组和第 3 组则出现了细胞毒性变性。结论：鼓室内施用 dex 负载的 CBGCH 已被证明可以提供针对 CP 诱导的耳毒性的功能和结构保护。
Objectives: The aim of this study was to investigate the protective effects of a sustained release form of dexamethasone (dex) loaded chitosan-based genipin-cross-linked hydrogel (CBGCH) in a guinea pig model of cisplatin (CP) induced hearing loss.Methods: Implantation of CBGCH was made by intratympanic (IT) injection. Ototoxicity was produced by intraperitoneal (IP) single dose of 14 mg/kg CP. Animals were randomly divided into four groups with 6 guinea pigs in each. Group 1 received only IP CP; group 2 received only IT dex-loaded CBGCH injections. Group 3 and group 4 received IP CP, plus IT nondrug CBGCH and IT dex-loaded CBGCH respectively 24 h prior to IP CP injections. Distortion product otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) measurements were obtained before the treatments and solely ABR measurements were done after 3 and 10 days. The ultrastructural effects were investigated by scanning electron microscopy (SEM) analysis.Results: The postCP ABR thresholds at 4, 8, 12, 16, 32 kHz frequencies were significantly better in group 4 than groups 1 and 3 (p < 0.05). The comparison of time effective ABR thresholds between groups 1 and 4 and between groups 3 and 4 showed significantly lower ABR thresholds in group 4 (p < 0.05). The SEM analysis showed that stereocilia of inner and outer hair cells were preserved in group 4, almost like group 2, whereas cytotoxic degenerations were noted in groups 1 and 3.Conclusions: Intratympanic administration of dex-loaded CBGCH has been shown to provide functional and structural protection against CP-induced ototoxicity.