TY - JOUR
T1 - Remotely controlled nanofluidic implantable platform for tunable drug delivery
AU - Di Trani, Nicola
AU - Silvestri, Antonia
AU - Bruno, Giacomo
AU - Geninatti, Thomas
AU - Chua, Corrine Ying Xuan
AU - Gilbert, April
AU - Rizzo, Giulia
AU - Filgueira, Carly S.
AU - Demarchi, Danilo
AU - Grattoni, Alessandro
N1 - Funding Information:
The membranes were provided by NanoMedical Systems. Funding support from the Houston Methodist Research Institute, NIH R21GM111544, NIH-NIGMS R01GM127558.
Publisher Copyright:
© 2019 The Royal Society of Chemistry.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2019/7/7
Y1 - 2019/7/7
N2 - Chronic diseases such as hypertension and rheumatoid arthritis are persistent ailments that require personalized lifelong therapeutic management. However, the difficulty of adherence to strict dosing schedule compromises therapeutic efficacy and safety. Moreover, the conventional one-size-fits-all treatment approach is increasingly challenged due to the intricacies of inter- and intra-individual variabilities. While accelerated technological advances have led to sophisticated implantable drug delivery devices, flexibility in dosage and timing modulation to tailor precise treatment to individual needs remains an elusive goal. Here we describe the development of a subcutaneously implantable remote-controlled nanofluidic device capable of sustained drug release with adjustable dosing and timing. By leveraging a low intensity electric field to modify the concentration driven diffusion across a nanofluidic membrane, the rate of drug administration can be increased, decreased or stopped via Bluetooth remote command. We demonstrate in vitro the release modulation of enalapril and methotrexate, first-line therapeutics for treatment of hypertension and rheumatoid arthritis, respectively. Further, we show reliable remote communication and device biocompatibility via in vivo studies. Unlike a pulsatile release regimen typical of some conventional controlled delivery systems, our implant offers a continuous drug administration that avoids abrupt fluctuations, which could affect response and tolerability. Our system could set the foundation for an on-demand delivery platform technology for long term management of chronic diseases.
AB - Chronic diseases such as hypertension and rheumatoid arthritis are persistent ailments that require personalized lifelong therapeutic management. However, the difficulty of adherence to strict dosing schedule compromises therapeutic efficacy and safety. Moreover, the conventional one-size-fits-all treatment approach is increasingly challenged due to the intricacies of inter- and intra-individual variabilities. While accelerated technological advances have led to sophisticated implantable drug delivery devices, flexibility in dosage and timing modulation to tailor precise treatment to individual needs remains an elusive goal. Here we describe the development of a subcutaneously implantable remote-controlled nanofluidic device capable of sustained drug release with adjustable dosing and timing. By leveraging a low intensity electric field to modify the concentration driven diffusion across a nanofluidic membrane, the rate of drug administration can be increased, decreased or stopped via Bluetooth remote command. We demonstrate in vitro the release modulation of enalapril and methotrexate, first-line therapeutics for treatment of hypertension and rheumatoid arthritis, respectively. Further, we show reliable remote communication and device biocompatibility via in vivo studies. Unlike a pulsatile release regimen typical of some conventional controlled delivery systems, our implant offers a continuous drug administration that avoids abrupt fluctuations, which could affect response and tolerability. Our system could set the foundation for an on-demand delivery platform technology for long term management of chronic diseases.
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U2 - 10.1039/c9lc00394k
DO - 10.1039/c9lc00394k
M3 - Article
C2 - 31169840
AN - SCOPUS:85068145634
VL - 19
SP - 2192
EP - 2204
JO - Lab on a Chip - Miniaturisation for Chemistry and Biology
JF - Lab on a Chip - Miniaturisation for Chemistry and Biology
SN - 1473-0197
IS - 13
ER -