Novel Superparamagnetic Microdevices Based on Magnetized PLGA/PLA Microparticles Obtained by Supercritical Fluid Emulsion and Coating by Carboxybetaine-Functionalized Chitosan Allowing the Tuneable Release of Therapeutics

Abstract When superparamagnetic nanoparticles (MAG) are loaded within microcarriers of thermosensitive and injectable biopolymers, "smart" microdevices are obtained: they respond to an external magnetic field through the release of any co-encapsulated molecules with a remote on-off control. Creating reliable and effective fabrication technologies for the production of these smart nano/microdevices remains a challenge. In this work, supercritical emulsion extraction technology is proposed for the fabrication of microcapsules with a core of poly-lactic-co-glycolic acid (PLGA) or polylactic acid (PLA) covered by carboxybetaine-functionalized chitosan ( f-chi ) and loaded with MAG (mean size of 6.5 ± 3.0 nm) and water-soluble fluorescein (Fluo). Fluo is co-encapsulated as a fluorescent marker for the release study. Microcarriers showed a mean size of 800 ± 60 nm with an encapsulation efficiency of up to 90%. The inversion of surface charge, after the f-chi coating, suggested the presence of a uniform functionalized surface available for further chemical linkage. The external chitosan layer had a thickness of 200 ± 50 nm. An excellent MAG dispersion was confirmed within the biopolymer matrix that was shown to be responsive to external magnetic field; indeed, Fluo was released over 3 or 5 days from PLGA or f-chi- PLGA microdevices into phosphate-buffered saline medium at 37°C, whereas remote on-off controlled release was achieved when an alternating magnetic field was applied.