Department of Dermatology, Mackay Memorial Hospital, Taipei, Taiwan; Mackay Medicine, Nursing and Management College, Taipei, Taiwan; Mackay Medical College, New Taipei City, Taiwan.
Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, Taiwan; Advanced Membrane Materials Research Center, Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, Taiwan.
Mater Sci Eng C Mater Biol Appl. 2020 Feb;107:110330. doi: 10.1016/j.msec.2019.110330. Epub 2019 Oct 23.
The present study focused on the development of electric stimuli drug release carrier based on transition metal dicgalcogenides. First, tungsten disulfide (WS) was exfoliated and functionalized using thiol chemistry with various thiol-terminated ligands such as thioglycolic acid (TGA), mercaptosuccinic acid (MSA), and 2-ethanethiol (2ET). The exfoliated WS underwent non-covalent coating with an electrically conductive polypyrrole (PPy) for functionalization, of which MSA-WS-PPy achieved the highest 5-FU (anticancer drug) loading. An electrically-stimulated drug release experiment showed that TGA-WS-PPy achieved a higher drug release (90%) than MSA-WS-PPy (70%) and 2ET-WS-Ppy (35%). The TGA-WS-PPy exhibited swelling/recombination between PPY and MSA-WS substrate under electrical stimulation, resulting in the highest 5-FU release. From the MTT assay result, there was no significant toxicity observed for TGA-WS-PPy-FU on HaCaT cells, indicating the biocompatibility of TGA-WS-PPy-FU in the absence of electrical stimulation. However, HaCaT cells died when incubated with TGA-WS-PPy-FU under electrical stimulation. Finally, Raman mapping studies for TGA-WS-PPy drug release in the skin of nude mice demonstrated that the carrier penetrated deeper into the skin of the mice while other systems failed to exhibit significant effects under electrical stimulation. The present study offers a novel approach in developing a non-invasive electrically-stimulated drug release system based on WS and an externally-controlled delivery model.
本研究专注于基于过渡金属二硫属化物的电刺激药物释放载体的开发。首先，通过硫醇化学将二硫化钨（WS）进行剥离和功能化，使用各种硫醇端基配体，如硫代乙醇酸（TGA）、巯基琥珀酸（MSA）和 2-乙硫醇（2ET）。剥离的 WS 经历了与导电聚吡咯（PPy）的非共价涂层以进行功能化，其中 MSA-WS-PPy 实现了最高的 5-FU（抗癌药物）负载。电刺激药物释放实验表明，TGA-WS-PPy 实现了比 MSA-WS-PPy（70%）和 2ET-WS-PPy（35%）更高的药物释放（90%）。TGA-WS-PPy 在电刺激下显示出 PPy 和 MSA-WS 基底之间的肿胀/重组，导致 5-FU 释放最高。从 MTT 测定结果来看，TGA-WS-PPy-FU 对 HaCaT 细胞没有观察到明显的毒性，表明在没有电刺激的情况下 TGA-WS-PPy-FU 的生物相容性。然而，当 HaCaT 细胞在电刺激下孵育含 TGA-WS-PPy-FU 的溶液时，细胞死亡。最后，对裸鼠皮肤中 TGA-WS-PPy 药物释放的 Raman 映射研究表明，载体在皮肤中渗透更深，而其他系统在电刺激下未能表现出明显的效果。本研究提供了一种基于 WS 和外部控制给药模型开发非侵入性电刺激药物释放系统的新方法。
