Environmental Responsive, Flexible Drug Delivery Chip - Design, Synthesis, and Characterization
Implanted therapy has played an important role in the field of neurobiology. A flexible magnetically-controllable drug delivery device was designed and fabricated using electrophoretic deposition of drug-carrying magnetic core-shell Fe3O4@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 0.5 mm 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. Based on the CNS disease, in order to give a sudden treatment as a response to the signal detected, a flexible electrically-controllable drug delivery device was designed and fabricated by incorporating electrically sensitive CHC (modified chitosan) hydrogels into the electrically-conductive transparent plastic container. Si#CHC hydrogel membrane was first prepared by the addition of genipin and TEOS with different weight ratios. In doing so, the thin and brittle hydrogel membranes with different cross-linked density or interpenetration degree displayed excellent swelling behavior and drug release behavior. Membrane-based device is fabricated by the combination of Si#CHC hydrogels and a transparent plastic container with a single small open hole designed as an outlet for drug elution and two rectangle-shaped platinum plate placed in a constant distance with two parallel sides. Upon the application of an electrical stimulus, the dehygrogenated ESM displayed the electrophoretic movement toward the anode and the electroosmosis toward the cathode. Since the opposite force restricted the net drug release from the hydrogels, the rate of drug release out of the device is decreased. Moreover, the increase of in the degree of which CHC hydrogels crosslinked with genipin leads to the stronger negatively charged polymer. The effect of electroosmotsis, which also facilitates gel shrinkage and force drugs to move out, is enhanced in the presence of the electric voltage. Hence the release profiles under elecltrical stimuli showed the more the contents of genipin, the faster the rate of drug release. Similarly, interpenetration of negatively charged TEOS inside the CHC chains provided more negative charge to the CHC networks. It also give rise to the enhancement of hydrogel shrinkage. So under the induction of the electric field, the rate of ESM release is increased when the content of TEOS is increased.