In situ microbubble-assisted, ultrasound-controlled release of superparamagnetic iron oxide nanoparticles from gastro-retentive tablets

[Display omitted] Organic and inorganic nanomaterials have shown great potential in drug delivery applications due to their unique physical and chemical properties. Orally administered nanoparticles have attracted great attention because it is acceptable, convenient, and safe. However, nanoparticles need to overcome numerous hurdles such as acidic gastric environment, the continuous secretion of mucus, and fast gastric emptying after being delivered via an oral route. Here, we used a stimuli-responsive and triggered release strategy for superparamagnetic iron oxide nanoparticles (SPIONPs)-loaded gastro-retentive tablets for in situ bubbles generation. These materials realize SPIOs controlled release and delivery specific to the stomach. The tablet formulation contains a foaming agent (sodium bicarbonate, NaHCO3), adhesive component (HPMC/carbomer 934 P (1:1)), filler (lactose/mannitol (10:1)) and SPIONPs. The in vitro bubble generation and SPIONPs released from the tablets were characterized. The ex vivo gastric adhesive ability, acoustic stimuli performance, and tissue penetration were further evaluated. The results show that when the fabricated tablets interacted with the acidic microenvironment, the carbon dioxide (CO2) could be generated and be captured by ultrasound (US) imaging. Simultaneous with bubble production, SPIONPs are released from the tablets to further control ultrasound-mediated force and deliver SPIONPs entering through the mucus layer. The SPIONPs were loaded in the tablets and could be released in a controllable way; thus, the magnetic resonance imaging (MRI) could also be used to monitor the tablet status and SPIONP delivery process. Therefore, SPIONPs-loaded gastro-retentive effervescent tablets offer effective release and absorption of nanoparticles in the gastric area and be imaged by MRI and US.