Leveraging nanochannels for universal, zero-order drug delivery in vivo

Ferrati, Silvia; Fine, Daniel H.; You, Junping; Rosa, Enrica De; Hudson, Lee; Zabre, Erika; Hosali, Sharath; Zhang, Li; Hickman, Catherine; Bansal, Shyam S.; Cordero‐Reyes, Andrea M.; Geninatti, Thomas; Sih, Juliana; Goodall, Randy; Palapattu, Ganesh S.; Kloc, Małgorzata; Ghobrial, Rafik M.; Ferrari, Mauro; Grattoni, Alessandro

doi:10.1016/j.jconrel.2013.09.028

Cited by 78 publications

(80 citation statements)

References 34 publications

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“…25–28 Using these nanochannel membranes, we have leveraged nanoconfinement to achieve zero-order release of pharmaceutical agents at clinically relevant rates over extended durations in vivo. 29–32 …”

Section: Introductionmentioning

confidence: 99%

Leveraging electrokinetics for the active control of dendritic fullerene-1 release across a nanochannel membrane

et al. 2015

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General adoption of advanced treatment protocols such as chronotherapy will hinge on progress in drug delivery technologies that provide precise temporal control of therapeutic release. Such innovation is also crucial to future medicine approaches such as telemedicine. Here we present a nanofluidic membrane technology capable of achieving active and tunable control of molecular transport through nanofluidic channels. Control was achieved through application of an electric field between two platinum electrodes positioned on either surface of a 5.7 nm nanochannel membrane designed for zero-order drug delivery. Two electrode configurations were tested: laser-cut foils and electron beam deposited thin-films, configurations capable of operating at low voltage (≤1.5 V), and power (100 nW). Temporal, reproducible tuning and interruption of dendritic fullerene 1 (DF-1) transport was demonstrated over multi-day release experiments. Conductance tests showed limiting currents in the low applied potential range, implying ionic concentration polarization (ICP) at the interface between the membrane’s micro- and nanochannels, even in concentrated solutions (≤ 1 M NaCl). The ability of this nanotechnology platform to facilitate controlled delivery of molecules and particles has broad applicability to next-generation therapeutics for numerous pathologies, including autoimmune diseases, circadian dysfunction, pain, and stress, among others.

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Section: Introductionmentioning

confidence: 99%

Leveraging electrokinetics for the active control of dendritic fullerene-1 release across a nanochannel membrane

et al. 2015

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“…This control is relevant to a broad spectrum of biomedical applications, including drug delivery (Desai et al 1999; Ferrati et al 2013, In press; Celia et al 2014), molecular sieving (Fu et al 2007), cell sorting (Gossett et al 2010), and cell transplantation (Desai et al 1998; Sabek et al 2013). In drug delivery, the ability to fine tune release profiles for specific therapeutic agents is highly beneficial in personalized treatments requiring dose titration or synchronization with the biological clock, the fundamental principle in chronotherapy (Smolensky and Peppas 2007; Youan 2010).…”

Section: Introductionmentioning

confidence: 99%

“…This platform has been specifically designed for hormone replacement, organ transplantation, and cancer prevention, among others (Fine et al 2010; Ferrati et al 2013, In press; Sih et al 2013). We hypothesized that drug release through our membrane could be modulated by using a low-voltage electrical potentials.…”

Section: Introductionmentioning

confidence: 99%

Impedance characterization, degradation, and in vitro biocompatibility for platinum electrodes on BioMEMS

Geninatti

Bruno

Barile

et al. 2015

Biomed Microdevices

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Fine control of molecular transport through microfluidic systems can be obtained by modulation of an applied electrical field across channels with the use of electrodes. In BioMEMS designed for biological fluids and in vivo applications, electrodes must be biocompatible, biorobust and stable. In this work, the analysis and characterization of platinum (Pt) electrodes integrated on silicon substrates for biomedical applications are presented. Electrodes were incorporated on the surface of silicon chips by adhesion of laminated Pt foils or deposited at 30°, 45° or 90° angle by e-beam or physical vapor (sputtering) methods. Electrical and physical properties of the electrodes were quantified and evaluated using electrical impedance spectroscopy and modelling of the electrode-electrolyte interfaces. Electrode degradation in saline solution at pH 7.4 was tested at room temperature and under accelerated conditions (90 °C), both in the presence and absence of an applied electrical potential. Degradation was quantified using atomic force microscopy (AFM) and inductively coupled plasma mass spectroscopy (ICP-MS). Biocompatibility was assessed by MTT proliferation assay with human dermal fibroblasts. Results demonstrated that the deposited electrodes were biocompatible with negligible material degradation and exhibited electrochemical behavior similar to Pt foils, especially for e-beam deposited electrodes. Finally, Pt electrodes e-beam deposited on silicon nanofabricated nanochannel membranes were evaluated for controlled drug delivery applications. By tuning a low applied electrical potential (<1.5 VDC) to the electrodes, temporal modulation of the dendritic fullerene 1 (DF-1) release from a source reservoir was successfully achieved as a proof of concept, highlighting the potential of deposited electrodes in biomedical applications.

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“…High aspect ratio tubular structures possibly may afford such release, however potential toxicity issues must be considered. Another route could utilize the concept of a "pepper pot" whereby the drug is stored in high quantity behind a release limiting pore size [284], however, scaling such a device down to the microscale for injectability would be no small feat. Lastly, the simple but effective concept of using microfluidic devices to form PLGA with an outer coating of alginate allowed near zero-order release of the model drug rifampicin in vitro as shown in Fig.…”

Section: Growth Factor Delivery Systemsmentioning

confidence: 99%

Prospects for polymer therapeutics in Parkinson's disease and other neurodegenerative disorders

Newland

Werner

et al. 2015

Progress in Polymer Science

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a b s t r a c tParkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons and represents a growing health burden to western societies. Like many neurodegenerative disorders the cause is unknown, however, as the pathogenesis becomes ever more elucidated, it is becoming clear that effective delivery is a key issue for new therapeutics. The versatility of today's polymerization techniques allows the synthesis of a wide range of polymer materials which hold great potential to aid in the delivery of small molecules, proteins, genetic material or cells. In this review, we capture the recent advances in polymer based therapeutics of the central nervous system (CNS). We place the advances in historical context and, furthermore, provide future prospects in line with newly discovered advancements in the understanding of PD and other neurodegenerative disorders. This review provides researchers in the field of polymer chemistry and materials science an up-to-date understanding of the requirements placed upon materials designed for use in the CNS aiding the focus of polymer therapeutic design.

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Leveraging nanochannels for universal, zero-order drug delivery in vivo

Cited by 78 publications

References 34 publications

Leveraging electrokinetics for the active control of dendritic fullerene-1 release across a nanochannel membrane

Leveraging electrokinetics for the active control of dendritic fullerene-1 release across a nanochannel membrane

Impedance characterization, degradation, and in vitro biocompatibility for platinum electrodes on BioMEMS

Prospects for polymer therapeutics in Parkinson's disease and other neurodegenerative disorders

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