Intracellular Uptake of Magnetic Nanocapsules with Ionic Chitosan Shells and Magnetically Triggered Cargo Release.

Introduction: Drug delivery systems typically need to be equipped with targeting moieties in order to be efficiently internalized by cells. Alternatively, magnetic nanoparticles (MNs) combined with active compounds may be driven by magnetic field to the site of action. Delivery of hydrophobic drugs using this approach is challenging as it would require coupling of MNs and hydrophobic environment within nanocarriers and triggering of the drug release.

Methods: We propose an approach enabling a magnetically induced forced uptake of core-shell nanocapsules carrying hydrophobic actives together with hydrophobized MNs. Such capsules, formed in a facile emulsification process, are composed of amphiphilic cationic or anionic chitosan (shell) and oil-dispersible MNs (oil core). The capsules were characterized using DLS, cryo-TEM. They were loaded with a model fluorescent dye, Nile Red, and pulled into cells applying a static magnetic field. Then, they were treated with an alternating magnetic field to disrupt the capsules thanks to the action of MNs.

Results: Cryo-TEM imaging confirmed the presence of MNs inside the capsules (d≈200 nm). Confocal microscopy imaging showed the efficient capsules' intracellular uptake only after exposition to static magnetic field (some spontaneous uptake was observed for anionic capsules). Then, application of alternating magnetic fields induced rapture of the capsules inside the cells and release of the cargo.

Discussion: This approach is very versatile as various lipophilic compounds could be encapsulated, then transported to desired tissues without active or passive targeting and kept there using static magnetic field, limiting undesired side effects of a therapy to the whole organism. The proposed capsules with MNs respond efficiently to magnetic field stimulation - they can be magnetically navigated into the cells and release their cargo after application of alternating magnetic field. This approach opens opportunities for controlled intracellular delivery of hydrophobic actives using easily applicable magnetic stimuli for both delivery and release.