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Abstract: A flexible drug delivery device was designed and fabricated using electrophoretic deposition of drug-carrying magnetic core-shell Fe3O4 at SiO2 nanoparticles onto an electrically conductive flexible PET substrate. The PET substrate was first patterned to a desired layout and subjected to deposition. In doing so, a uniform and nanoporous membrane could be produced. After lamination of the patterned membranes, a final chip-like device of thickness less than 0.5mm is formed that is used for controlled delivery of an anti-epileptic drug, i.e., ethosuximide (ESM). The release of useful drugs can be controlled by directly modulating the magnetic field, and the chip is capable of demonstrating a variety of release profiles (i.e., slow release, sustained release, step-wise release and burst release profiles). These profiles can follow a wide spectrum of patterns ranging from zero to pulsatile release kinetics depending on the mode of magnetic operation. When the magnetic field was removed, the release behavior was instantly ceased, and vice versa. A preliminary in-vivo study using Long–Evans rat model has demonstrated a significant reduction in spike-wave discharge after the ESM was burst released from the chip under the same magnetic induction as in-vitro, indicating the potential application of the drug delivery chip. The flexible and membrane-like drug delivery chip utilizes drug-carrying magnetic nanoparticles as the building blocks that ensure a rapid and precise response to magnetic stimulus. Moreover, the flexible chip may offer advantages over conventional drug delivery devices by improvement of dosing precision, ease of operation, wider versatility of elution pattern, and better compliance. [Copyright &y& Elsevier]

We developed a surfactant-free method utilizing amifostine to stably link a targeting ligand (Herceptin) to amphiphilic gelatin (AG)-iron oxide@calcium phosphate (CaP) nanoparticles with hydrophobic curcumin (CUR) and hydrophilic doxorubicin (DOX) encapsulated in the AG core and CaP shell (AGIO@CaP-CD), respectively. This multi-functional nanoparticle system has a pH-sensitive CaP shell and degradable amphiphilic gelatin (AG) core, which enables controllable sequential release of the two drugs. The dual-targeting system of AGIO@CaP-CD (HER-AGIO@CaP-CD) with a bioligand and magnetic targeting resulted in significantly elevated cellular uptake in HER2-overexpressing SKBr3 cells and more efficacious therapy than delivery of targeting ligand alone due to the synergistic cell multi-drug resistance/apoptosis-inducing effect of the CUR and DOX combination. This nanoparticle combined with Herceptin and iron oxide nanoparticles not only provided a dual-targeting functionality, but also encapsulated CUR and DOX as a dual-drug delivery system for the combination therapy. This study further demonstrated that the therapeutic efficacy of this dual-targeting co-delivery system can be improved by modifying the application duration of magnetic targeting, which makes this combination therapy system a powerful new tool for in vitro/in vivo cancer therapy, especially for HER2-positive cancers. [ABSTRACT FROM AUTHOR]