比较圆窗膜透气性增强剂:动物研究。

IF 4.7 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Jae Sang Han, Ye Lin Kim, Kyusun Park, Ji Hyung Lim, Hong-Lim Kim, So Young Park, Shi Nae Park
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引用次数: 0

摘要

鼓膜内(IT)给药地塞米松(DEX)广泛用于治疗内耳疾病;然而,其治疗效果受到圆窗膜(RWM)渗透性差的限制。本研究旨在评估和比较三种药物——组胺(HIS)、3%高渗生理盐水(3% HS)和碳酸钠(SC)——作为佐剂在小鼠模型中增强RWM通透性和改善IT-DEX递送的有效性和安全性。在给药后注射DEX,用高效液相色谱法测定淋巴周围DEX浓度,用免疫荧光法测定Corti器官中DEX受体的表达。透射电镜观察RWM的结构变化,听觉脑干反应(ABR)测试评估听觉功能。与对照组相比,所有三种增强剂都显著增加了淋巴周围DEX浓度,3% HS显示出最高水平。3% HS也诱导了最大的DEX受体表达,仅引起短暂的RWM结构改变,无永久性损伤。尽管药物输送增强,但治疗组间ABR阈值恢复无统计学差异。这些研究结果表明,3% HS是IT药物递送测试中最有效的佐剂,尽管在该模型中,内耳药物渗透的增强不一定转化为功能恢复的改善。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comparing Round Window Membrane Permeability Enhancers: An Animal Study.

Intratympanic (IT) delivery of dexamethasone (DEX) is widely used for treating inner ear disorders; however, its therapeutic efficacy is limited by poor permeability of the round window membrane (RWM). This study aimed to evaluate and compare the efficacy and safety of three pharmacological agents-histamine (HIS), 3% hypertonic saline (3% HS), and sodium caprate (SC)-as adjuvants for enhancing RWM permeability and improving IT-DEX delivery in a murine model. Following IT administration of each permeability enhancer followed by DEX injection, perilymph DEX concentrations were measured using ultra-high-performance liquid chromatography, and DEX receptor expression in the organ of Corti was assessed by immunofluorescence. Structural changes in the RWM were examined by transmission electron microscopy, and auditory function was evaluated using auditory brainstem response (ABR) testing. All three enhancers significantly increased perilymph DEX concentrations compared to controls, with 3% HS demonstrating the highest levels. 3% HS also induced the greatest DEX receptor expression and caused only transient RWM structural alterations without permanent damage. Despite enhanced drug delivery, no statistically significant differences in ABR threshold recovery were observed among treatment groups. These findings demonstrate that 3% HS is the most effective adjuvant among those tested for IT drug delivery, although enhanced inner ear drug penetration does not necessarily translate to improved functional recovery in this model.

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来源期刊
CiteScore
9.60
自引率
2.20%
发文量
248
审稿时长
50 days
期刊介绍: The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.
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