经荧光地塞米松标记研究的鼓室内应用药物的渗透增强剂。
Permeation Enhancers for Intratympanically-applied Drugs Studied Using Fluorescent Dexamethasone as a Marker.
机构信息
Department of Otolaryngology, Eye, Ear, Nose, & Throat Hospital, Fudan University, Shanghai, China.
Department of Otolaryngology, Washington University School of Medicine, St Louis, Missouri.
出版信息
Otol Neurotol. 2018 Jun;39(5):639-647. doi: 10.1097/MAO.0000000000001786.
HYPOTHESIS
Entry of locally applied drugs into the inner ear can be enhanced by chemical manipulations.
BACKGROUND
Perilymph drug concentrations achieved by intratympanic applications are well below the applied concentration due to limited entry through the round window (RW) membrane and stapes. Chemical manipulations to increase entry permeability could increase the effectiveness of drug therapy with local applications.
METHODS
Dexamethasone-fluorescein (F-dex) was used as an entry marker. F-dex was applied to the RW niche of guinea pigs as a 20 μL bolus of 1 mM solution. After a 1 hour application, 10 samples of perilymph were collected sequentially from the lateral semicircular canal, allowing F-dex distribution throughout the perilymph to be quantified. Entry was also measured with the applied solution additionally containing dimethyl sulfoxide (DMSO), N-methylpyrrolidone (NMP), saponin, caprate, benzyl alcohol (BA) or poloxamer 407 (P407). Combinations of saponin or BA with P407 were also compared.
RESULTS
In control experiments, F-dex entered the inner ear slowly at both the RW and stapes. The total F-dex recovered in all 10 samples from each animal averaged 2.1 pMoles for controls, 1.71 pMoles for 17% P407, 3.70 pMoles for caprate, 8.04 pMoles for DMSO, 16.32 pMoles for NMP, 31.0 pMoles for saponin, and 67.3 pMoles for 4% BA. Entry with DMSO, NMP, saponin and 4% BA were all significantly higher than the controls (one-way ANOVA).
CONCLUSION
These studies confirm that entry of drugs into the ear can be markedly enhanced with the use of chemical permeation-enhancing agents.
假设
通过化学处理可以增强局部应用药物进入内耳的能力。
背景
由于通过圆窗（RW）膜和镫骨进入的药物有限，经鼓室内应用达到的外淋巴药物浓度远低于应用浓度。增加进入通透性的化学处理可以提高局部应用药物治疗的效果。
方法
地塞米松-荧光素（F-dex）被用作进入标记物。将 F-dex 作为 1mM 溶液的 20μL 脉冲施加到豚鼠的 RW 窝中。在 1 小时的应用后，从外侧半规管顺序收集 10 个外淋巴样本，以定量 F-dex 在整个外淋巴中的分布。还通过应用溶液另外包含二甲亚砜（DMSO）、N-甲基吡咯烷酮（NMP）、皂苷、辛酸、苯甲醇（BA）或泊洛沙姆 407（P407）来测量进入。还比较了皂苷或 BA 与 P407 的组合。
结果
在对照实验中，F-dex 在 RW 和镫骨处缓慢进入内耳。从每个动物的所有 10 个样本中回收的总 F-dex 平均值为对照的 2.1 皮摩尔，17% P407 的 1.71 皮摩尔，辛酸的 3.70 皮摩尔，DMSO 的 8.04 皮摩尔，NMP 的 16.32 皮摩尔，皂苷的 31.0 皮摩尔，和 4% BA 的 67.3 皮摩尔。DMSO、NMP、皂苷和 4% BA 的进入均明显高于对照（单因素方差分析）。
结论
这些研究证实，通过使用化学渗透增强剂可以显著增强药物进入耳朵的能力。
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