Abstract
Individualized long-term management of chronic pathologies remains an elusive goal despite recent progress in drug formulation and implantable devices. The lack of advanced systems for therapeutic administration that can be controlled and tailored based on patient needs precludes optimal management of pathologies, such as diabetes, hypertension, rheumatoid arthritis. Several triggered systems for drug delivery have been demonstrated. However, they mostly rely on continuous external stimuli, which hinder their application for long-term treatments. In this work, we investigated a silicon nanofluidic technology that incorporates a gate electrode and examined its ability to achieve reproducible control of drug release. Silicon carbide (SiC) was used to coat the membrane surface, including nanochannels, ensuring biocompatibility and chemical inertness for long-term stability for in vivo deployment. With the application of a small voltage (≤ 3 V DC) to the buried polysilicon electrode, we showed in vitro repeatable modulation of membrane permeability of two model analytes—methotrexate and quantum dots. Methotrexate is a first-line therapeutic approach for rheumatoid arthritis; quantum dots represent multi-functional nanoparticles with broad applicability from bio-labeling to targeted drug delivery. Importantly, SiC coating demonstrated optimal properties as a gate dielectric, which rendered our membrane relevant for multiple applications beyond drug delivery, such as lab on a chip and micro total analysis systems (µTAS).
Highlights
Chronic pathologies affect nearly half of the population worldwide [1,2] and represent one of the leading causes of death and disability [3]
We investigated the performance of a silicon nanofluidic membrane that uses electrostatic gating [32] to modulate the transport of charged molecules by modifying nanochannel permeability
Prior to investigating the electrical performance of the membranes, we sought to analyze the quality of the membrane fabrication process (Figure 1)
Summary
Chronic pathologies affect nearly half of the population worldwide [1,2] and represent one of the leading causes of death and disability [3]. The pathophysiology of most chronic diseases is determined by circadian biological cycles [12], which have a significant impact on the efficacy of treatment and associated adverse effects [13]. This is the case for pathologies, such as diabetes and metabolic disorders [14], hypertension, psychiatric and neurodegenerative conditions [15], rheumatoid arthritis [16], and chronic pain [17], to name a few, where the timing of drug administration is key to elicit the intended therapeutic effect
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