| 1. |
- Seitanidou, Maria S, 1985-, et al.
(author)
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Graphene-Enabled Electrophoretic Ion Pump Delivery Devices
- 2022
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In: Advanced Materials Interfaces. - : Wiley. - 2196-7350. ; 9:12
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Journal article (peer-reviewed)abstract
- Organic electronic ion pumps (OEIPs) have been investigated as a promising solution for precise local delivery of biological signaling compounds. OEIP miniaturization provides several advantages, ranging from better spatiotemporal control of delivery to reduced invasiveness for implanted devices. One miniaturization route is to develop OEIPs based on polyelectrolyte-filled capillary fibers. These devices can be easily brought into proximity of targeted cells and tissues and could be considered as a starting point for other "iontronic" implants. To date, OEIPs and other such iontronics exhibit a limited electrode capacity as they generally rely on poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) electrodes. While this material is well studied and viable in mixed ion-electron systems, its bulk capacitance is limited by eventual redox reactions. Graphene is an excellent alternative for high-performance electrodes and low-cost solution-processed graphene derivatives are particularly promising, exhibiting high charge mobility and ideal structural properties (lightness, flexibility). Here, the application of solution-processed reduced graphene oxide (RGO) as high-performance driving electrodes for OEIPS is presented. RGO electrodes are characterized and compared with standard PEDOT:PSS (and Ag/AgCl) electrodes. The RGO exhibits greater charge storage capacity and thus increased operational lifetime. The graphene-enabled OEIPs exhibit improved neurotransmitter transport, without imposing limitations to the applied current level.
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| 2. |
- Abrahamsson, Tobias, et al.
(author)
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Investigating the role of polymer size on ionic conductivity in free-standing hyperbranched polyelectrolyte membranes
- 2021
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In: Polymer. - : Elsevier. - 0032-3861 .- 1873-2291. ; 223
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Journal article (peer-reviewed)abstract
- Polymer-based ion exchange membranes (IEMs) are utilized for many applications such as in water desalination, energy storage, fuel cells and in electrophoretic drug delivery devices, exemplified by the organic electronic ion pump (OEIP). The bulk of current research is primarily focused on finding highly conductive and stable IEM materials. Even though great progress has been made, a lack of fundamental understanding of how specific polymer properties affect ionic transport capabilities still remains. This leads to uncertainty in how to proceed with synthetic approaches for designing better IEM materials. In this study, an investigation of the structure-property relationship between polymer size and ionic conductivity was performed by comparing a series of membranes, based on ionically charged hyperbranched polyglycerol of different polymer sizes. Observing an increase in ionic conductivity associated with increasing polymer size and greater electrolyte exclusion, indi-cating an ionic transportation phenomenon not exclusively based on membrane electrolyte uptake. These findings further our understanding of ion transport phenomena in semi-permeable membranes and indicate a strong starting point for future design and synthesis of IEM polymers to achieve broader capabilities for a variety of ion transport-based applications.
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| 3. |
- Arbring Sjöström, Theresia, et al.
(author)
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A Decade of Iontronic Delivery Devices
- 2018
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In: Advanced Materials Technologies. - : Wiley. - 2365-709X. ; 3:5
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Research review (peer-reviewed)abstract
- In contrast to electronic systems, biology rarely uses electrons as the signal to regulate functions, but rather ions and molecules of varying size. Due to the unique combination of both electronic and ionic/molecular conductivity in conjugated polymers and polyelectrolytes, these materials have emerged as an excellent tool for translating signals between these two realms, hence the field of organic bioelectronics. Since organic bioelectronics relies on the electron-mediated transport and compensation of ions (or the ion-mediated transport and compensation of electrons), a great deal of effort has been devoted to the development of so-called "iontronic" components to effect precise substance delivery/transport, that is, components where ions are the dominant charge carrier and where ionic-electronic coupling defines device functionality. This effort has resulted in a range of technologies including ionic resistors, diodes, transistors, and basic logic circuits for the precisely controlled transport and delivery of biologically active chemicals. This Research News article presents a brief overview of some of these "ion pumping" technologies, how they have evolved over the last decade, and a discussion of applications in vitro, in vivo, and in plantae.
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| 4. |
- Bernacka Wojcik, Iwona, et al.
(author)
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Flexible Organic Electronic Ion Pump for Flow-Free Phytohormone Delivery into Vasculature of Intact Plants
- 2023
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In: Advanced Science. - : WILEY. - 2198-3844. ; 10:14
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Journal article (peer-reviewed)abstract
- Plant vasculature transports molecules that play a crucial role in plant signaling including systemic responses and acclimation to diverse environmental conditions. Targeted controlled delivery of molecules to the vascular tissue can be a biomimetic way to induce long distance responses, providing a new tool for the fundamental studies and engineering of stress-tolerant plants. Here, a flexible organic electronic ion pump, an electrophoretic delivery device, for controlled delivery of phytohormones directly in plant vascular tissue is developed. The c-OEIP is based on polyimide-coated glass capillaries that significantly enhance the mechanical robustness of these microscale devices while being minimally disruptive for the plant. The polyelectrolyte channel is based on low-cost and commercially available precursors that can be photocured with blue light, establishing much cheaper and safer system than the state-of-the-art. To trigger OEIP-induced plant response, the phytohormone abscisic acid (ABA) in the petiole of intact Arabidopsis plants is delivered. ABA is one of the main phytohormones involved in plant stress responses and induces stomata closure under drought conditions to reduce water loss and prevent wilting. The OEIP-mediated ABA delivery triggered fast and long-lasting stomata closure far away from the delivery point demonstrating systemic vascular transport of the delivered ABA, verified delivering deuterium-labeled ABA.
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| 5. |
- Handl, Verena, et al.
(author)
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Continuous iontronic chemotherapy reduces brain tumor growth in embryonic avian in vivo models
- 2024
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In: Journal of Controlled Release. - : ELSEVIER. - 0168-3659 .- 1873-4995. ; 369, s. 668-683
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Journal article (peer-reviewed)abstract
- Local and long-lasting administration of potent chemotherapeutics is a promising therapeutic intervention to increase the efficiency of chemotherapy of hard-to-treat tumors such as the most lethal brain tumors, glioblastomas (GBM). However, despite high toxicity for GBM cells, potent chemotherapeutics such as gemcitabine (Gem) cannot be widely implemented as they do not efficiently cross the blood brain barrier (BBB). As an alternative method for continuous administration of Gem, we here operate freestanding iontronic pumps - "GemIPs" - equipped with a custom-synthesized ion exchange membrane (IEM) to treat a GBM tumor in an avian embryonic in vivo system. We compare GemIP treatment effects with a topical metronomic treatment and observe that a remarkable growth inhibition was only achieved with steady dosing via GemIPs. Daily topical drug administration (at the maximum dosage that was not lethal for the embryonic host organism) did not decrease tumor sizes, while both treatment regimes caused S-phase cell cycle arrest and apoptosis. We hypothesize that the pharmacodynamic effects generate different intratumoral drug concentration profiles for each technique, which causes this difference in outcome. We created a digital model of the experiment, which proposes a fast decay in the local drug concentration for the topical daily treatment, but a long-lasting high local concentration of Gem close to the tumor area with GemIPs. Continuous chemotherapy with iontronic devices opens new possibilities in cancer treatment: the long-lasting and highly local dosing of clinically available, potent chemotherapeutics to greatly enhance treatment efficiency without systemic side-effects. Significance statement: Iontronic pumps (GemIPs) provide continuous and localized administration of the chemotherapeutic gemcitabine (Gem) for treating glioblastoma in vivo. By generating high and constant drug concentrations near the vascularized growing tumor, GemIPs offer an efficient and less harmful alternative to systemic administration. Continuous GemIP dosing resulted in remarkable growth inhibition, superior to daily topical Gem application at higher doses. Our digital modelling shows the advantages of iontronic chemotherapy in overcoming limitations of burst release and transient concentration profiles, and providing precise control over dosing profiles and local distribution. This technology holds promise for future implants, could revolutionize treatment strategies, and offers a new platform for studying the influence of timing and dosing dependencies of already -established drugs in the fight against hard -to -treat tumors.
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| 6. |
- Seitanidou, Maria S, et al.
(author)
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Modulating Inflammation in Monocytes Using Capillary Fiber Organic Electronic Ion Pumps
- 2019
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In: Advanced Healthcare Materials. - : WILEY. - 2192-2640 .- 2192-2659. ; 8:19
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Journal article (peer-reviewed)abstract
- An organic electronic ion pump (OEIP) delivers ions and drugs from a source, through a charge selective membrane, to a target upon an electric bias. Miniaturization of this technology is crucial and will provide several advantages, ranging from better spatiotemporal control of delivery to reduced invasiveness for implanted OEIPs. To miniaturize OEIPs, new configurations have been developed based on glass capillary fibers filled with an anion exchange membrane (AEM). Fiber capillary OEIPs can be easily implanted in proximity to targeted cells and tissues. Herein, the efficacy of such a fiber capillary OEIP for modulation of inflammation in human monocytes is demonstrated. The devices are located on inflammatory monocytes and local delivery of salicylic acid (SA) is initiated. Highly localized SA delivery results in a significant decrease in cytokine (tumor necrosis factor alpha and interleukin 6) levels after lipopolysaccharide stimulation. The findings-the first use of such capillary OEIPs in mammalian cells or systems-demonstrate the utility of the technology for optimizing transport and delivery of different therapeutic substances at low concentrations, with the benefit of local and controlled administration that limits the adverse effect of oral/systemic drug delivery.
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| 7. |
- Seitanidou, Maria S, et al.
(author)
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Overcoming transport limitations in miniaturized electrophoretic delivery devices
- 2019
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In: Lab on a Chip. - : Royal Society of Chemistry. - 1473-0197 .- 1473-0189. ; 19:8, s. 1427-1435
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Journal article (peer-reviewed)abstract
- Organic electronic ion pumps (OEIPs) have been used for delivery of biological signaling compounds, at high spatiotemporal resolution, to a variety of biological targets. The miniaturization of this technology provides several advantages, ranging from better spatiotemporal control of delivery to reduced invasiveness for implanted OEIPs. One route to miniaturization is to develop OEIPs based on glass capillary fibers that are filled with a polyelectrolyte (cation exchange membrane, CEM). These devices can be easily inserted and brought into close proximity to targeted cells and tissues and could be considered as a starting point for other fiber-based OEIP and iontronic technologies enabling favorable implantable device geometries. While characterizing capillary OEIPs we observed deviations from the typical linear current-voltage behavior. Here we report a systematic investigation of these irregularities by performing experimental characterizations in combination with computational modelling. The cause of the observed irregularities is due to concentration polarization established at the OEIP inlet, which in turn causes electric field-enhanced water dissociation at the inlet. Water dissociation generates protons and is typically problematic for many applications. By adding an ion-selective cap that separates the inlet from the source reservoir this effect is then, to a large extent, suppressed. By increasing the surface area of the inlet with the addition of the cap, the concentration polarization is reduced which thereby allows for significantly higher delivery rates. These results demonstrate a useful approach to optimize transport and delivery of therapeutic substances at low concentrations via miniaturized electrophoretic delivery devices, thus considerably broadening the opportunities for implantable OEIP applications.
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| 8. |
- Strakosas, Xenofon, 1985-, et al.
(author)
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An electronic proton-trapping ion pump for selective drug delivery
- 2021
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In: Science Advances. - : American Association for the Advancement of Science. - 2375-2548. ; 7:5
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Journal article (peer-reviewed)abstract
- The organic electronic ion pump (OEIP) delivers ions and charged drugs from a source electrolyte, through a charge-selective membrane, to a target electrolyte upon an electric bias. OEIPs have successfully delivered γ-aminobutyric acid (GABA), a neurotransmitter that reduces neuronal excitations, in vitro, and in brain tissue to terminate induced epileptic seizures. However, during pumping, protons (H+), which exhibit higher ionic mobility than GABA, are also delivered and may potentially cause side effects due to large local changes in pH. To reduce the proton transfer, we introduced proton traps along the selective channel membrane. The traps are based on palladium (Pd) electrodes, which selectively absorb protons into their structure. The proton-trapping Pd-OEIP improves the overall performance of the current state-of-the-art OEIP, namely, its temporal resolution, efficiency, selectivity, and dosage precision.
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| 9. |
- Waldherr, Linda, et al.
(author)
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Targeted Chemotherapy of Glioblastoma Spheroids with an Iontronic Pump
- 2021
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In: Advanced Materials Technologies. - : Wiley. - 2365-709X. ; 6:5
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Journal article (peer-reviewed)abstract
- Successful treatment of glioblastoma multiforme (GBM), the most lethal tumor of the brain, is presently hampered by (i) the limits of safe surgical resection and (ii) "shielding" of residual tumor cells from promising chemotherapeutic drugs such as Gemcitabine (Gem) by the blood brain barrier (BBB). Here, the vastly greater GBM cell-killing potency of Gem compared to the gold standard temozolomide is confirmed, moreover, it shows neuronal cells to be at least 10(4)-fold less sensitive to Gem than GBM cells. The study also demonstrates the potential of an electronically-driven organic ion pump ("GemIP") to achieve controlled, targeted Gem delivery to GBM cells. Thus, GemIP-mediated Gem delivery is confirmed to be temporally and electrically controllable with pmol min(-1) precision and electric addressing is linked to the efficient killing of GBM cell monolayers. Most strikingly, GemIP-mediated GEM delivery leads to the overt disintegration of targeted GBM tumor spheroids. Electrically-driven chemotherapy, here exemplified, has the potential to radically improve the efficacy of GBM adjuvant chemotherapy by enabling exquisitely-targeted and controllable delivery of drugs irrespective of whether these can cross the BBB.
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