Spatiotemporally Controllable Chemical Delivery Via Hydrogel Electroosmotic Pump
Authors: SUN Yunhao , Li Chenxing , Moriyama Natsuho , Wang Gaobo , Tottori Soichiro , Nishizawa Matsuhiko 
Published: December 2024

Objectives

Chemical delivery is an important basic operation in various biomedical fields, including in vitro cell analysis for drug development and in vivo drug management using implanted and wearable devices.[1] Traditional controllable drug delivery system (DDS) uses pressure-driven microfluidics and external pressure pumps to apply water pressure to the nozzles of microchannels, which makes it hard to instantaneously transmit pressure via flexible soft microchannels, resulting in low controllability of chemical transportation.[2] EOF is a solvent convection motion generated by the preferential electrophoretic movement of mobile counter cations (or anions) through negatively (or positively) charged microchannels (Fig. 1a). In this regard, the EOF-based DDS is electrically controlled and multifunctional, enabling the transportation of most chemicals, regardless of their charge and size.[3] Although some of the established EOF-based pumps used porous materials sandwiched between electrodes to prevent current from flowing to the outside, one of the electrodes is close to the target, which raises concerns about the impact of electrolysis. In addition, many traditional electroosmotic pumps have external electrodes, and the drug transportation may be accompanied by unnecessary electrical stimulation of target cells and tissues.[4] In this study, we developed an EOF-driven chemical delivery system generated by the combination of anionic and cationic hydrogels, as shown in Fig. 1b. Since the EOF directions in anion hydrogel (A-hydrogel) and cationic hydrogel (C-hydrogel) are opposite due to the cations and anions that preferentially move, the enhanced EOF at the outlet of the device can effectively transport chemicals without any external ion current.

Results and Discussion

Utilizing the inherent flexibility and water-retentive properties of the hydrogel, two slender tubular delivery devices (in straight state and tied state respectively) were fabricated to enable insertion into intricate in vivo structures. As illustrated in Fig
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1c, the EOF rate, discerned as the linear slope of the plots, was assessed under ± 0.5 mA current conditions for both the straight (blue plot) and tied (red plot) states. The flow rates exhibited negligible disparity between the two states during both injection and suction maneuvers. These findings underscore the remarkable adaptability of the developed thin-film device, capable of accommodating the substantial deformations requisite for precise localized drug delivery within complex organ structures. Fig
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1d shows the assessment of rhodamine B (RhB) ejection into 0.3 wt% agarose hydrogel cubes, selected for its resemblance to brain tissue properties. Notably, the quantity of RhB ejected into the agarose medium exhibited a discernible correlation with applied currents ranging from 0 to 0.3 mA, suggesting the application potential for controlled in vivo chemical dispensation.

Conclusion

In this study, a novel concept of a chemical delivery system by focusing on the EOFs generated in the A- and C-hydrogels in opposite directions from each other was introduced. The utilization of A/C-hydrogel combinations in the construction of tubular devices facilitated the creation of a closed-loop system for the generation of ionic current. This unique design characteristic allowed for chemical delivery to target cells and tissues without reliance on external flows of ion current. This feature is important, as it extends beyond muscles and nerves to encompass an array of cell and tissue types that can respond to ionic currents. Moreover, the versatility of EOF-based systems is underscored by their applicability to a diverse range of chemicals, irrespective of their charge and size. This inherent adaptability lends considerable practical advantages to EOF-based DDS, enhancing their utility across various biomedical applications.

Reference

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Fig
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1 (a) Schematic illustration of electroosmotic flow. (b) Schematic of EOF-driven chemical delivery system combined of anionic and cationic hydrogels. (c) EOF flow rate in the straight state (blue plot) and tied state (red plot) at ± 0.5 mA. (d) Demonstration of RhB delivery into 0.3 wt% agarose hydrogel by applying currents ranging from 0 to 0.3 mA for 10 min.

Figure 1