Enhancement of Trans-Tympanic Drug Delivery by Pharmacological Induction of Inflammation

• DOI: 10.1021/acs.molpharmaceut.2c00959
• Publication Date: 2023-01-12T14:21:28Z
• Authors: Zipei Zhang; Xiyu Li; Rong Yang; Kathleen Cullion; Laura Prugneau; Daniel S. Kohane
• Keywords: Inflammation; 0301 basic medicine; Otitis Media; 03 medical and health sciences; Tympanic Membrane; Humans; 3. Good health; Histamine; Anti-Bacterial Agents

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.