Permeation Enhancers for Intratympanically-applied Drugs Studied Using Fluorescent Dexamethasone as a Marker
Permeation Enhancers for Intratympanically-applied Drugs Studied Using Fluorescent Dexamethasone as a Marker
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使用荧光地塞米松作为标记物研究鼓室内药物的渗透增强剂
DOI：
10.1097/mao.0000000000001786
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发表时间：
2018-06-01
影响因子：
2.1
通讯作者：
Salt, Alec N.
中科院分区：
文献类型：
--
作者：
Li, Wei;Hartsock, Jared J.;Salt, Alec N.
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 20L bolus of 1mM 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.
