Matoori Simon, Roveri Maurizio, Tiefenboeck Peter, Romagna Annatina, Wuerthinger Olha, Kolokythas Orpheus, Froehlich Johannes M
Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Vladimir-Prelog-Weg 1-5/10, 8093, Zurich, Switzerland.
Clinical Research Group, Klus Apotheke Zurich, Zurich, Switzerland.
Eur Radiol Exp. 2019 Mar 5;3(1):11. doi: 10.1186/s41747-019-0090-9.
Externally controlling and monitoring drug release at a desired time and location is currently lacking in the gastrointestinal tract. The aim of the study was to develop a thermoresponsive wax-coated capsule and to trigger its release upon applying a magnetic resonance imaging (MRI)-guided high-intensity focused ultrasound (HIFU) pulse.
Capsules containing a lyophilised gadolinium-based contrast agent (GBCA) were coated with a 1:1 (mass/mass) mixture of lanolin and cetyl alcohol (melting point ≈43 °C) and exposed to simulated gastric and intestinal fluids (United States Pharmacopoeia) at 37 °C for 2 and 24 h, respectively. In a HIFU gel phantom, wax-coated capsules (n = 3) were tracked based on their T1- and T2-hypointensity by 1.5-T T1- and T2-weighted MRI pre- and post-exposure to an MRI-guided HIFU pulse.
Lanolin/cetyl alcohol-coated capsules showed high resistance to simulated gastrointestinal fluids. In a gel phantom, an MRI-guided HIFU pulse punctured the wax coating, resulting in the hydration and release of the encapsulated lyophilised GBCA and yielding a T1-hyperintense signal close to the wax-coated capsule.
We provide the proof-of-concept of applying a non-invasive MRI-guided HIFU pulse to actively induce the disintegration of the wax-coated capsule, and a method to monitor the release of the cargo via T1-weighted MRI based on the hydration of an encapsulated lyophilised GBCA. The wax-coated capsule platform enables temporally and spatially supertargeted drug release via the oral route and promises to address a currently unmet clinical need for personalised local therapy in gastrointestinal diseases such as inflammatory bowel diseases and cancer.
目前在胃肠道中尚缺乏在期望的时间和位置对外控和监测药物释放的方法。本研究的目的是开发一种热敏蜡包衣胶囊，并在磁共振成像（MRI）引导的高强度聚焦超声（HIFU）脉冲作用下触发其释放。
含有冻干钆基造影剂（GBCA）的胶囊用羊毛脂和十六醇（熔点约43°C）的1:1（质量/质量）混合物包衣，并分别在37°C下于模拟胃液和肠液（美国药典）中暴露2小时和24小时。在HIFU凝胶体模中，基于蜡包衣胶囊在暴露于MRI引导的HIFU脉冲前后的T1和T2低信号强度对其（n = 3）进行跟踪。
羊毛脂/十六醇包衣的胶囊对模拟胃肠液表现出高抗性。在凝胶体模中，MRI引导的HIFU脉冲刺穿了蜡涂层，导致包封的冻干GBCA水合并释放，在靠近蜡包衣胶囊处产生T1高信号。
我们提供了应用无创MRI引导的HIFU脉冲来主动诱导蜡包衣胶囊崩解的概念验证，并提供了一种基于包封的冻干GBCA水合作用通过T1加权MRI监测货物释放的方法。蜡包衣胶囊平台能够通过口服途径实现时空超靶向药物释放，并有望满足目前在炎症性肠病和癌症等胃肠疾病中个性化局部治疗尚未满足的临床需求。
