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适当地将疏水性、氧化还原活性药物掺入聚乳酸-石墨烯纳米片复合体内,生成用于电刺激治疗的 3D 打印药用贴剂。

Suitably Incorporated Hydrophobic, Redox-Active Drug in Poly Lactic Acid-Graphene Nanoplatelet Composite Generates 3D-Printed Medicinal Patch for Electrostimulatory Therapeutics.

机构信息

Department of Biological Sciences & Bioengineering, Indian Institute of Technology Kanpur, Kalyanpur, Kanpur, 208016, India.

The Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology Kanpur, Kalyanpur, Kanpur, 208016, India.

出版信息

Langmuir. 2024 Jun 11;40(23):11858-11872. doi: 10.1021/acs.langmuir.3c03338. Epub 2024 May 27.

DOI:10.1021/acs.langmuir.3c03338
PMID:38801374
Abstract

Polymer carbon composites have been reported for improved mechanical, thermal and electrical properties to provide reduced side effect by 3D printing personalized biomedical drug delivery devices. But control on homogeneity in loading and release of dopants like carbon allotropes and drugs, respectively, in the bulk and on the surface has always been a challenge. Herein, we are reporting a methodological cascade to achieve a model, customizable, 3D printed, homogeneously layered and electrically stimulatory, PLA-Graphene nanoplatelet (-PLGR) based drug delivery device, called 3D--MediPatch. The medicinal patch has been prepared by 3D-printing a --PLGR composite obtained by incorporating a redox active model drug, niclosamide (Nic) in -PLGR. The composite of --PLGR was characterized in three sequentially complex forms─composite film, hot melt extruded (HME) filament, and 3D printed (3DP) patches to understand the effect of filament extrusion and 3D-printing processes on --PLGR composite and overall drug incorporation efficiency and control. The incorporation of graphene was found to improve the homogeneity of the drug, and the hot melt extrusion improved the dispersion of drug and graphene fillers in the composite. The electroresponsive drug release from the --PLGR composite was found to be controllably accelerated compared to the drug release by diffusion, in simulated buffer condition. The released drug concentration was found to reach within the IC50 range for malignant melanoma cell (A375) and showed selectively, with reduced effects in noncancerous, fibroblast cells (NIH3T3). Further, the feasibility of application for this system was assessed in generating personalized 3D--MediPatch for skin, liver and spleen tissues in scenario. It showed excellent feasibility and efficacy of the 3D--MediPatch in controlled and personalized release of drugs during electrostimulation. Thus, a model platform, 3D--MediPatch, could be achieved by suitably incorporating a hydrophobic, redox-active drug (niclosamide) in poly lactic acid-graphene nanoplatelet composite for electrostimulatory therapeutics with reduced side effects.

摘要

聚合物碳复合材料已被报道具有改善的机械、热和电性能,通过 3D 打印个性化生物医学药物输送装置来提供减少副作用。但是,对掺杂剂(如碳同素异形体和药物)在本体和表面的均匀装载和释放的控制一直是一个挑战。在此,我们报告了一种方法级联,以实现一种模型、可定制、3D 打印、均匀分层和电刺激的 PLA-石墨烯纳米片(-PLGR)基药物输送装置,称为 3D--MediPatch。该药用贴片是通过 3D 打印由还原活性模型药物尼氯酰胺(Nic)掺入-PLGR 制备的-PLGR 复合材料而制备的。-PLGR 复合材料以三种依次复杂的形式进行了表征——复合膜、热熔挤出(HME)长丝和 3D 打印(3DP)贴片,以了解长丝挤出和 3D 打印工艺对-PLGR 复合材料和整体药物掺入效率和控制的影响。发现掺入石墨烯可提高药物的均匀性,而热熔挤出可改善药物和石墨烯填料在复合材料中的分散性。与扩散释放相比,在模拟缓冲条件下,-PLGR 复合材料的电响应药物释放被发现可得到可控加速。释放的药物浓度被发现达到恶性黑色素瘤细胞(A375)的 IC50 范围内,并表现出选择性,对非癌细胞(NIH3T3)的影响较小。此外,还评估了该系统在场景中用于皮肤、肝脏和脾脏组织的个性化 3D--MediPatch 生成中的应用可行性。它在电刺激下的药物控制和个性化释放中表现出出色的可行性和功效。因此,可以通过在聚乳酸-石墨烯纳米片复合材料中适当掺入疏水性、氧化还原活性药物(尼氯酰胺)来实现模型平台 3D--MediPatch,用于具有减少副作用的电刺激治疗。

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