以下文章来源于中科院天津工业生物所 ，作者李泽华
研究背景
离子电渗透，是一种离子流在电场力的驱动下在介质中有向扩散的物理过程。基于此原理，离子化的药物分子在电场力的作用下可主动透过皮肤的生物屏障，提高透皮和吸收的效果。然而目前基于离子电渗透的经皮给药技术或装置，都需依赖外接电源或金属基电池来驱动获得电场力，在安全性和便捷性上不甚理想。酶燃料电池是一种新型的燃料电池，可通过生物酶在电极上的催化，将廉价底物中的化学能直接转化为电能，在柔性可穿戴电子器件供电和传感等方面展示了应用潜力。鉴于其良好的产电性能、优异的安全性和生物相容性，酶燃料电池可提供产生电场力所需的清洁、安全、低成本的电能，进而促进药物经皮吸收，有望为基于离子电渗透的经皮给药技术提供了新的能源解决方案。
研究成果
中科院天津工业生物技术研究所体外合成生物学中心张以恒研究员和朱之光研究员团队，首次将柔性可穿戴的酶燃料电池与面膜相结合，在无纺布基底上制备了基于葡萄糖和葡萄糖氧化酶的酶燃料电池，并证实了其可驱动离子电渗透以促进面膜相关有效成分的经皮吸收。首先，研究人员为了最大化离子电渗透效果同时保持材料的透水透气以及生物相容性，尝试了多种在无纺布基底上制备柔性电极的材料和方法，解决了电子中介体脱落、酶载量低、接触电阻大、由于碳纳米材料导致的面膜发黑等问题，所制备的酶燃料电池可以10 mM葡萄糖为底物产出约0.4 V的电压和23 μW/cm2的功率密度。其次，研究人员以罗丹明、烟酰胺、阿司匹林和熊果苷为例，对这些分子的经皮吸收效果进行了定性和定量的分析，基于Franz透皮实验的结果证明该离子电渗透面膜在15分钟内可提高2到3倍的分子经皮渗透量。此外，该面膜在基于小鼠急性足炎症模型的活体动物经皮给药实验中也表现出类似的促渗效果。最后，通过红细胞溶血实验和L929活性实验均证实了该面膜材料具有良好的生物相容性。这些结果初步证明了酶燃料电池驱动的离子电渗透面膜技术的可行性，为后续进一步提升其性能和可应用性奠定了基础，也为酶燃料电池驱动其他基于离子电渗透的经皮给药技术的开发提供了参考。相关研究以“Enzymatic biofuel cell-powered iontophoretic facial mask for enhanced transdermal drug delivery”为题发表在Biosensors & Bioelectronics期刊上。
研究亮点
1. 首次将酶燃料电池与面膜应用巧妙结合，建立了基于无纺布基底的柔性酶燃料电池制备工艺。
2. 获得了酶燃料电池驱动的离子电渗透面膜，展现出良好的药物经皮促渗效果和生物相容性。
图文导读
Figure 1. Preparation of the EBFC-powered iontophoretic facial mask. (a) Electron transfer from enzyme to current collector. (b) Fabrication of the flexible bioanode with a three-layer structure. (c) A screen-printed flexible EBFC on the non-woven fabric. (d) Prototype of the EBFC-powered iontophoretic facial mask. (e) Working mechanism of iontophoresis.
Figure 2. (a–d) Construction and characterization of the conductive silver layer. (a) SEM patterns of the silver flakes. (b) SEM images of the conductive silver layer on the non-woven fabric after curing of silver paste. (c) Optimization of the silver concentration. (d) Stability of the conductive silver layer under aqueous conditions. (e–h) Synthesis and characterization of mediator-decorated CNTI(e) XPS patterns of mediator-modified CNTs and pristine CNTs. (f) CVs of CNT-NH2-FC and CNT-NH2 in 0.1 M PBS (pH 7.2). (g) Optimization of mediator addition. (h) Full-length absorption of the discarded supernatant during the synthesis process. (i–n) Immobilization of nanomaterial on the surface of the conductive silver layer. (i–l) Optimization of polyurethane addition. (m) Morphology of the non-woven fabric with a silver layer and a nanomaterial layer. (n) Smooth surface of the conductive silver layer with partially buried silver flakes.
Figure 3. (a) Optimization of enzyme immobilization. (b) CVs of the prepared enzymatic electrode with or without 10 mM glucose in 0.1 M PBS. (c) Power density of the prepared flexible EBFC with or without 10 mM glucose in 0.1 M PBS. (d) Within-group and between-group variability of the flexible EBFC with or without 10 mM glucose. (e) Stability of the flexible EBFC. (f) Effects of substrate volume on the working voltage of the EBFC.
Figure 4. (a) Proof-of-concept experiment. (b) Fluorescence intensity of the RhB on the pig skin surface. (c) Transdermal drug delivery experiment through a Franz cell. (d) The amount of permeated nicotinamide within 15 min under different electric intensities of the EBFC. (e) The amount of permeated nicotinamide within 15 min under the same electric intensities of DC power. (f) The relationship between electrode spacing and infiltration area. (g) The permeated amount of nicotinamide, aspirin, and arbutin within 15 min in the non-iontophoresis and EBFC-powered iontophoresis groups.
Figure 5. (a) Transdermal drug delivery in living animals. (b) Edema data of the three groups before administration and 5 h after administration. (c) Thickness of the dorsal tissue of healthy and inflamed paws in the three groups. (d–f) Histopathological slides of the healthy paw in the control, transdermal, and iontophoresis groups. (g–h) Histopathological slides of the inflammation model paw in the control, transdermal, and iontophoresis groups.
Figure 6. (a) Evaluation of the blood compatibility of mediator-decorated nanomaterial. (b) Toxicity evaluation of mediator-decorated nanomaterial to L929 cells. (c) Fluorescence images of L929 cell viability after 24 h of co-culture with different concentrations of extract.
总结与展望
本文中，作者成功设计并制备了基于无纺布基底的柔性酶燃料电池及由其驱动的离子电渗透的面膜原型，该面膜展现出良好的药物经皮促渗效果和生物相容性。初步证明了酶燃料电池驱动的离子电渗透面膜的可行性，为后续进一步提升其性能和可应用性奠定了基础，也为开拓酶燃料电池更多应用提供了新思路。
文章链接
Enzymatic biofuel cell-powered iontophoretic facial mask for enhanced transdermal drug delivery
https://www.sciencedirect.com/science/article/abs/pii/S0956566322010594
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