Abstract
Sustained release and replenishment of the drug depot are essential for the long-term functionality of implantable drug-delivery devices. This study demonstrates the use nanoporous gold (np-Au) thin films for in-plane transport of fluorescein (a small-molecule drug surrogate) over large (mm-scale) distances from a distal reservoir to the site of delivery, thereby establishing a constant flux of molecular release. In the absence of halides, the fluorescein transport is negligible due to a strong non-specific interaction of fluorescein with the pore walls. However, in the presence of physiologically relevant concentration of ions, halides preferentially adsorb onto the gold surface, minimizing the fluorescein–gold interactions and thus enabling in-plane fluorescein transport. In addition, the nanoporous film serves as an intrinsic size-exclusion matrix and allows for sustained release in biofouling conditions (dilute serum). The molecular release is reproducibly controlled by gating it in response to the presence of halides at the reservoir (source) and the release site (sink) without external triggers (e.g., electrical and mechanical).
Highlights
Implantable drug delivery platforms are emerging as powerful technologies for treating and managing a wide range of medical conditions, including cancer, diabetes, and epilepsy [1,2,3,4,5,6,7]
One class of drug delivery technology is based on the use of macro-scale infusion pumps or miniaturized microelectromechanical systems (MEMS)-based pumps, where the delivery segment and the reservoir can be both implanted [11,12,13]
Since np-Au thin filmsphenomenon can be patterned translated microfabrication into multiple electrode arrays [41,69], where np-Au electrode traces can transport ventional techniques, the in-plane transport phenomenon can be transsmall molecules along the traces from the external electrical pads to the individual electrode sites for subsequent molecular release
Summary
Implantable drug delivery platforms are emerging as powerful technologies for treating and managing a wide range of medical conditions, including cancer, diabetes, and epilepsy [1,2,3,4,5,6,7] These drug delivery modalities have shown promise in overcoming several pharmaceutical challenges by improving permeation across the blood–brain barrier [8], reducing systemic side effects through targeted delivery at the site of interest [9], and maintaining the delivery dose within the therapeutic window for high efficacy and low toxicity [10]. One class of drug delivery technology is based on the use of macro-scale infusion pumps or miniaturized microelectromechanical systems (MEMS)-based pumps, where the delivery segment (e.g., cannula) and the reservoir can be both implanted [11,12,13] In both cases, the pharmaceuticals are delivered in a liquid vehicle solution by convective means, which leads to the problem of potentially damaging increase of local pressure in the target tissue. There are still obstacles, such as biofouling of the nanostructured material, controlling the release rate, and the unavoidable depletion of drug molecules in a fully implanted system
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