Bansal Mahima, Raos Brad, Aqrawe Zaid, Wu Zimei, Svirskis Darren
School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand.
Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand.
Acta Biomater. 2022 Jan 1;137:124-135. doi: 10.1016/j.actbio.2021.10.010. Epub 2021 Oct 10.
Recent advances in drug delivery have made it possible to release bioactive agents from neural implants specifically to local tissues. Conducting polymer coatings have been explored as a delivery platform in bioelectronics, however, their utility is restricted by their limited loading capacity and stability. This study presents the fabrication of a stable conducting polymer hydrogel (CPH), comprising the hydrogel gelatin methacrylate (GelMA), and conducting polymer polypyrrole (PPy) for the electrically controlled delivery of glutamate (Glu). The hybrid GelMA/PPy/Glu can be photolithographically patterned and covalently bonded to an electrode. Fourier-transform infrared (FTIR) analysis confirmed the interpenetrating nature of PPy through the GelMA hydrogels. Electrochemical polymerisation of PPy/Glu through the GelMA hydrogels resulted in a significant increase in the charge storage capacity as determined by cyclic voltammetry (CV). Long-term electrochemical and mechanical stability was demonstrated over 1000 CV cycles and extracts of the materials were cytocompatible with SH-SY5Y neuroblastoma cell lines. Release of Glu from the CPH was responsive to electrical stimulation with almost five times the amount of Glu released upon constant reduction (-0.6 V) compared to when no stimulus was applied. Notably, GelMA/PPy/Glu was able to deliver almost 14 times higher amounts of Glu compared to conventional PPy/Glu films. The described CPH coatings are well suited in implantable drug delivery applications and compared to conducting polymer films can deliver higher quantities of drug in response to mild electrical stimulus. STATEMENT OF SIGNIFICANCE: Conducting polymer hydrogels (CPH) have been explored for the electrically controlled release of bioactives from implantable devices. Typically, the conducting polymer component does not fully penetrate the hydrogel. We report, for the first time, a completely interpenetrating CPH allowing for the full benefits of the composite material to be realised, the hydrogels provide a reservoir for drug delivery, and conducting polymer renders the material responsive to electrical stimulation for drug release. We report a CPH for the electrically controlled delivery of glutamate (excitatory neurotransmitter) where several-fold more glutamate can be delivered compared to conducting polymer films. The described CPH coatings are well suited for use in bioelectronic devices to deliver large quantities of drug in response to mild electrical stimulus.
药物递送领域的最新进展使得从神经植入物向局部组织特异性释放生物活性剂成为可能。导电聚合物涂层已被探索作为生物电子学中的递送平台,然而,它们的效用受到其有限的负载能力和稳定性的限制。本研究展示了一种稳定的导电聚合物水凝胶(CPH)的制备,该水凝胶由甲基丙烯酸明胶(GelMA)水凝胶和导电聚合物聚吡咯(PPy)组成,用于电控递送谷氨酸(Glu)。杂化的GelMA/PPy/Glu可以通过光刻进行图案化,并与电极共价结合。傅里叶变换红外(FTIR)分析证实了PPy通过GelMA水凝胶的互穿性质。通过GelMA水凝胶对PPy/Glu进行电化学聚合,导致循环伏安法(CV)测定的电荷存储容量显著增加。在1000次CV循环中展示了长期的电化学和机械稳定性,并且材料提取物与SH-SY5Y神经母细胞瘤细胞系具有细胞相容性。与未施加刺激时相比,CPH中Glu的释放对电刺激有响应,在持续还原(-0.6 V)时释放的Glu量几乎是未施加刺激时的五倍。值得注意的是,与传统的PPy/Glu薄膜相比,GelMA/PPy/Glu能够递送的Glu量几乎高出14倍。所描述的CPH涂层非常适合用于可植入药物递送应用,并且与导电聚合物薄膜相比,能够在温和电刺激下递送更高量的药物。重要性声明:导电聚合物水凝胶(CPH)已被探索用于从可植入装置中电控释放生物活性物质。通常,导电聚合物组分不能完全穿透水凝胶。我们首次报道了一种完全互穿的CPH,能够实现复合材料的全部益处,水凝胶为药物递送提供了储存库,导电聚合物使材料对药物释放的电刺激产生响应。我们报道了一种用于电控递送谷氨酸(兴奋性神经递质)的CPH,与导电聚合物薄膜相比,其能够递送的谷氨酸量高出数倍。所描述的CPH涂层非常适合用于生物电子装置,以在温和电刺激下递送大量药物。