A 3D-Printed Modular Microreservoir for Drug Delivery

Abstract

<jats:p>Reservoir-based drug delivery microsystems have enabled novel and effective drug delivery concepts in recent decades. These systems typically comprise integrated storing and pumping components. Here we present a stand-alone, modular, thin, scalable, and refillable microreservoir platform as a storing component of these microsystems for implantable and transdermal drug delivery. Three microreservoir capacities (1, 10, and 100 µL) were fabricated with 3 mm overall thickness using stereolithography 3D-printing technology, enabling the fabrication of the device structure comprising a storing area and a refill port. A thin, preformed dome-shaped storing membrane was created by the deposition of parylene-C over a polyethylene glycol sacrificial layer, creating a force-free membrane that causes zero forward flow and insignificant backward flow (2% of total volume) due to membrane force. A septum pre-compression concept was introduced that enabled the realization of a 1-mm-thick septa capable of ~65000 leak-free refill punctures under 100 kPa backpressure. The force-free storing membrane enables using normally-open micropumps for drug delivery, and potentially improves the efficiency and precision of normally-closed micropumps. The ultra-thin septum reduces the thickness of refillable drug delivery devices, and is capable of thousands of leak-free refills. This modular and scalable device can be used for drug delivery in different laboratory animals and humans, as a sampling device, and for lab-on-a-chip and point-of-care diagnostics applications.</jats:p>

Chemically-Gated and Sustained Molecular Transport through Nanoporous Gold Thin Films in Biofouling Conditions

“…This would be highly useful for both in vitro and in vivo cases, where the source reservoir does not need to be kept sterile, while the sink reservoir can remain sterile for cell culture or tissue contact. This would further allow for using the source reservoir for replenishing pharmaceuticals (via several methods involving hypodermic needle-accessible membranes [ 2 , 13 , 71 ]) without having the remove the implanted devices. In addition, np-Au’s antimicrobial properties [ 72 ], compatibility with biomolecules and tissue [ 38 ], and reproducibility in manufacturing [ 41 ] fulfill aspects of the Safe-by-Design approach for nanobiomaterial development, which highlights np-Au’s potential for clinical translation [ 73 ].…”

“…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.…”

3D Printing as a Promising Tool in Personalized Medicine

“…A novel, hybrid manufacturing process was developed for drug delivery systems incorporated with drug depots, where the matrix of the DDS was generated by SLA and loading of drug depots was done using inkjet printing ( 106 ). Microreservoirs for implantable and transdermal delivery were developed ( 107 ). Goyanes and associates developed salicylic acid–based anti-acne masks using FDM and SLA.…”

A Wirelessly Controlled Scalable 3D-Printed Microsystem for Drug Delivery

“…Here, we present a low-cost, miniature, thin, programmable, and wirelessly controlled microsystem for implantable and transdermal drug delivery, fabricated with 3D-printing technology and enabling scalability for applications ranging from small animal models to clinical use in children and adults. We review the designs of the microreservoir and the micropump, which were published recently [35,36], along with describing modifications of the micropump fabrication process to improve long-term application suitability. The micropump and microreservoir were integrated in a single embodiment using 3Dprinting technology.…”

“…The entire interior surface of the microreservoir is coated with parylene-C, providing a class VI biocompatible environment for long-term drug storage. 3D-printing technology enables scalability in the range of 1-100 µL and integration to alternative pumping mechanisms by minimal change in the design [35].…”