Mucoadhesive Air Microbubbles With Sustained Antibiotic Release for Ultrasound-Guided Intrauterine Infusion Therapy of Endometritis

Endometritis, a common gynecological disease caused by ascending bacterial infection, is a leading cause of infertility. Currently, the clinical treatment relies primarily on antibiotic therapy, administered via intravenous injection, oral administration, or local delivery (e.g., intrauterine infusion). Nevertheless, intravenous injection aggravates hepatic and renal burdens, whereas oral administration elicits gastrointestinal reactions; intrauterine infusion suffers from drug leakage from the uterus due to gravity. Therefore, we developed mucoadhesive doxycycline hydrochloride-loaded air microbubbles (Mad-Doxy-MBs) for intrauterine infusion therapy of endometritis to overcome these limitations. The results showed that Mad-Doxy-MBs exhibited an ultrasound contrast-enhancement property so that they could be tracked by clinicians under ultrasound to achieve their precise localization on the endometrium when infused transvaginally. Subsequently, Mad-Doxy-MBs adhered to the endometrial surface and continuously released Doxy, exhibiting robust bactericidal and anti-inflammatory capacities. Compared with daily oral Doxy administration, two once-weekly intrauterine infusions of Mad-Doxy-MBs achieved superior therapeutic efficacy against endometritis while exhibiting markedly lower gastrointestinal toxicity. This drug delivery platform that integrates the properties of ultrasound visualization, mucoadhesion, and sustained drug release offers a clinically translatable strategy for intrauterine infusion therapy of endometritis and opens new avenues for precise and long-term drug delivery in other luminal diseases.