An MRI-guided HIFU-triggered wax-coated capsule for supertargeted drug release: a proof-of-concept study.

ABSTRACT: 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.

SUBMITTER: Matoori S 

PROVIDER: S-EPMC6401064 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature