Enhancement of Trans-Tympanic Drug Delivery by Pharmacological Induction of Inflammation.
Enhancement of Trans-Tympanic Drug Delivery by Pharmacological Induction of Inflammation.
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通过药理学诱导炎症增强经鼓室药物输送。
DOI：
10.1021/acs.molpharmaceut.2c00959
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发表时间：
2023
影响因子：
4.9
通讯作者：
Kohane,DanielS
中科院分区：
文献类型：
--
作者：
Zhang,Zipei;Li,Xiyu;Yang,Rong;Cullion,Kathleen;Prugneau,Laura;Kohane,DanielS
直接穿过鼓膜（TM）输送药物可以消除全身暴露于治疗中耳炎的抗生素，这是儿科医生开抗生素的最常见原因。在这里，我们假设诱导 TM 炎症可以增强穿过 TM 的药物通量。我们证明，通过促炎剂组胺治疗，环丙沙星穿过 TM 的流量大大增加。这种增强作用被组胺受体 1 阻断剂的同时治疗所阻断。用组胺治疗 TM 能够增强药物通量，足以根除龙猫体内的中耳炎，但前提是在用抗生素治疗之前施用组胺。
Drug delivery directly across the tympanic membrane (TM) could eliminate systemic exposure to antibiotics prescribed for otitis media, the most common reason for pediatricians to prescribe antibiotics. Here, we hypothesized that inducing inflammation of the TM could enhance drug flux across the TM. We demonstrated that the flux of ciprofloxacin across the TM was greatly increased by treatment with the proinflammatory agent histamine. That enhancement was blocked by concurrent treatment with blockers of histamine receptor 1. Treatment of the TM with histamine was able to enhance drug flux sufficiently to eradicate otitis media in vivo in chinchillas, but only if the histamine was applied prior to treatment with antibiotics.