Background

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.

Methods

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.

Results

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.

Conclusion

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.

中文翻译：

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MRI 引导的 HIFU 触发蜡涂层胶囊用于超靶向药物释放：一项概念验证研究。

背景

目前胃肠道中缺乏在所需时间和位置外部控制和监测药物释放的方法。该研究的目的是开发一种热敏蜡涂层胶囊，并在应用磁共振成像（MRI）引导的高强度聚焦超声（HIFU）脉冲时触发其释放。

方法

含有冻干钆基造影剂 (GBCA) 的胶囊涂有羊毛脂和鲸蜡醇（熔点约 43 °C）1:1（质量/质量）混合物，并暴露于模拟胃液和肠液（美国药典） ）在 37°C 下分别保持 2 和 24 小时。在 HIFU 凝胶体模中，在暴露于 MRI 引导的 HIFU 脉冲之前和之后，通过 1.5-T T1 和 T2 加权 MRI，根据其 T1 和 T2 低血压来跟踪蜡涂层胶囊（n = 3 ）。

结果

羊毛脂/鲸蜡醇涂层胶囊对模拟胃肠液表现出高耐受性。在凝胶体模中，MRI 引导的 HIFU 脉冲刺穿蜡涂层，导致封装的冻干 GBCA 水合和释放，并在蜡涂层胶囊附近产生 T1 高信号。

结论

我们提供了应用非侵入性 MRI 引导 HIFU 脉冲主动诱导蜡涂层胶囊崩解的概念验证，以及一种通过基于水合的 T1 加权 MRI 监测货物释放的方法封装的冻干 GBCA。蜡包衣胶囊平台能够通过口服途径在时间和空间上实现超靶向药物释放，并有望解决目前未满足的胃肠道疾病（如炎症性肠病和癌症）个性化局部治疗的临床需求。