基于catechol的化学物质,用于通过基于水凝的微针贴片技术对低血糖反应的-葡萄糖的输送
Amin GhavamiNejad1, Jackie Fule Liu1, Sako Mirzaie1
1Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie L. Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
Nature communications
|April 1, 2025
概括
一种新的微针贴片监测葡萄糖并释放-葡萄糖,以预防糖尿病患者的低血糖症. 这种智能水凝贴片使用甲基醇和酸化学物质来进行响应性药物输送.
科学领域:
- 生物材料科学 生物材料科学
- 药物输送系统 药物输送系统
- 糖尿病 技术 技术
背景情况:
- 低血糖是胰岛素依赖糖尿病患者的一个关键风险.
- 目前的葡萄糖监测和胰岛素输送系统在预防低血糖方面存在局限性.
- 需要响应性药物输送系统来管理血糖波动.
研究的目的:
- 开发和评估一种"智能"微针 (MN) 贴片,用于输送一种血糖升高剂的葡萄糖反应.
- 为了利用甲基醇和酸化学物质来释放低血糖引起的药物.
- 为了证明MN贴片在预防低血糖症方面的 in vivo 疗效.
主要方法:
- 制造一种基于水凝的自我交叉连接的微针贴片.
- 整合了catechol和酸的功能,用于感知葡萄糖和药物结合.
- 微针贴片和药物释放动态的体外表征.
- 在1型糖尿病小鼠接受过量胰岛素挑战的体内评估.
主要成果:
- 微针贴片显示了对葡萄糖反应的-葡萄糖 (Z-GCN) 的释放.
- 实验室研究证实了葡萄糖,甲基醇和Z-GCN之间的竞争性结合机制.
- 在体内研究表明,在糖尿病大鼠中,高达6小时有效预防低血糖症.
- 该系统成功地提供了Z-GCN,以应对降低葡萄糖水平.
结论:
- 开发的微针贴片提供了一种有希望的保护措施,防止胰岛素依赖糖尿病的低血糖.
- 甲基醇-金属离子竞争性结合机制对蛋白质/的治疗作用有着广泛的影响.
- 这种智能水凝MN贴片代表了闭环糖尿病管理系统的重大进步.
相关概念视频
Hypoglycemia and Glucagon
143
Without prolonged fasting, healthy individuals maintain blood glucose levels above 3.5 mM due to a well-adapted neuroendocrine counterregulatory system that effectively prevents acute hypoglycemia, a potentially life-threatening condition. The primary clinical scenarios for hypoglycemia encompass diabetes treatment, inappropriate production of endogenous insulin or insulin-like substances by tumors, and the use of glucose-lowering agents in non-diabetic individuals. Notably, hypoglycemia in the...
143
Oral Hypoglycemic Agents: Glinides
114
Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
114
Insulin Formulations: Types and Delivery
143
Insulin preparations are categorized by their duration of action into short-acting and long-acting types. Two strategies are used to modify insulin's absorption and pharmacokinetic profile: slowing the absorption post-subcutaneous injection, or altering human insulin's amino acid sequence or protein structure. These changes retain the insulin's ability to bind to the insulin receptor, but alter its behavior in solution or after injection.
Short-acting insulins are divided into...
Short-acting insulins are divided into...
143
Insulin: Biosynthesis, Chemistry, and Preparation
322
The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
322
Glucagon-like Receptor Agonists
272
Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
272
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
1.0K
The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
Insulin and C-peptide are...
Insulin and C-peptide are...
1.0K


