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葡萄糖响应性胰高血糖素微针贴片的缩微制造。

Shrinking Fabrication of a Glucose-Responsive Glucagon Microneedle Patch.

机构信息

Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA.

Department of Chemistry, College of Sciences, Northeastern University, Shenyang, 110819, China.

出版信息

Adv Sci (Weinh). 2022 Oct;9(28):e2203274. doi: 10.1002/advs.202203274. Epub 2022 Aug 11.

Abstract

A microdevice that offers glucagon supplements in a safe, non-invasive, and glucose-responsive manner is ideal for avoiding fatal hypoglycemia consequences from insulin overdosage during daily diabetes treatment. However, mold-assisted microfabrication of biomedical materials or devices typically needs high-resolution laser ablation to scale down structural design. In addition, the majority of the polymeric drug delivery materials being used to fabricate devices are dissolvable or deformable in aqueous environments, which restricts washing-based cleaning and purification procedures post shape fixation. This study leverages the design flexibility of 3D printing-assisted mold casting and presents a shrinking microfabrication approach that allows subsequent washing procedures to remove toxic monomer residues during polymerization. The feasibility of this approach is demonstrated by developing a glucose-responsive transdermal glucagon microneedle patch through matrix volume change-mediated release kinetic control. Shown in the type 1 diabetic mouse model, this transdermal patch can reverse the occurrence of hypoglycemia while lowering the risk of monomer residue-induced irritation during treatment. Freeing from the restrain of molding resolution for microstructure design, this shrinking methodology further provides an insight into post-fabrication purifications of biomedical materials.

摘要

一种能够以安全、非侵入和葡萄糖响应的方式提供胰高血糖素补充的微设备对于避免糖尿病日常治疗中胰岛素过量导致的致命低血糖后果是理想的。然而,用于制造生物医学材料或设备的模具辅助微制造通常需要高分辨率的激光烧蚀来缩小结构设计。此外,用于制造设备的大多数聚合物药物输送材料在水基环境中是可溶解或可变形的,这限制了形状固定后的基于清洗的清洁和纯化程序。本研究利用 3D 打印辅助模具铸造的设计灵活性,并提出了一种收缩微制造方法,允许在聚合过程中通过后续的清洗程序去除有毒单体残留物。通过通过基质体积变化介导的释放动力学控制来开发葡萄糖响应的透皮胰高血糖素微针贴片,证明了这种方法的可行性。在 1 型糖尿病小鼠模型中,这种透皮贴片可以逆转低血糖的发生,同时降低治疗过程中单体残留物引起的刺激的风险。这种收缩方法不受微结构设计的模具分辨率的限制,进一步为生物医学材料的后制造纯化提供了思路。

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