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相关概念视频

Insulin Formulations: Types and Delivery01:27

Insulin Formulations: Types and Delivery

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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.
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Oral Hypoglycemic Agents: Glinides01:06

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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...
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Insulin: Biosynthesis, Chemistry, and Preparation01:25

Insulin: Biosynthesis, Chemistry, and Preparation

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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...
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Glucagon-like Receptor Agonists01:24

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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...
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Insulin: Dosing Regimen and Adverse Effects01:16

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Insulin-replacement therapy usually includes both long-acting insulin (basal) and short-acting insulin (to cater to postprandial needs). In a diverse group of type 1 diabetes patients, the average daily insulin dose is typically 0.5-0.7 units/kg body weight. However, obese patients and pubertal adolescents may need more due to insulin resistance.
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Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of...
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Surface Engineering of Pancreatic Islets with a Heparinized StarPEG Nanocoating
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胰岛素延长释放来自PLA-PEG立体复合纳米粒子.

Tovi Shapira-Furman1, Abraham J Domb1

  • 1The Hebrew University of Jerusalem, Faculty of Medicine, School of Pharmacy, Jerusalem, 91120, Israel.

Macromolecular bioscience
|November 29, 2023
PubMed
概括

这项研究引入了一种新的纳米配方,用于使用立体复杂化机制的和蛋白质药物. 开发的胰岛素纳米颗粒在糖尿病小鼠中显示了持续释放和有效的治疗结果.

关键词:
聚乙烯,PLA-PEG,PLA-PEG,PLA-PEG,PLA-PEG,PLA-PEG,PLA-PEG,PLA-PEG,PLA-PEG,PLA-PEG,PLA-PEG,PLA-PEG,PLA-PEG,PLA-PEG,PLA-PEG,PLA-PEG,PLA-PEG,PLA-PEG,PLA-PEG,PEG-PEG,PEG-PEG,PEG-PEG,PEG-PEG,PEG-PEG,PEG-PEG,PEG-PEG,PEG-PEG,PEG-PEG,PEG-PEG,PEG-PEG,PEG-PEG,PEG-PEG-PEG,PEG-PEG-PEG-PEG-PEG-PEG-PEG-PEG有控制释放的释放.药物输送是药物输送的过程.在这种情况下,胰岛素胰岛素.这是一种类药物药物.这是一个刻板的复杂.

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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
  • 纳米技术 纳米技术

背景情况:

  • 和蛋白质疗法在稳定性和可控交付方面面临挑战.
  • 现有的药物输送方法经常与这些生物分子固有的不稳定性作斗争.
  • 开发有效的输送系统对于治疗成功至关重要.

研究的目的:

  • 开发一种新的纳米配方,用于控制和蛋白质疗法的药物输送.
  • 为了提高稳定性,在水性介质中利用立体复合机制.
  • 评估开发系统的体外和体内性能.

主要方法:

  • 通过立体复合,在水性介质中使用聚D-乳酸) -聚乙烯甘醇 (D-PLA-PEG) 和胰岛素制造纳米粒子.
  • 纳米粒子大小 (≈400 nm) 和自发形成因凸适应性而形成的特征.
  • 在体释放研究中,酸盐缓冲溶液 (PBS) 在pH7.4.4下释放.
  • 在17周内对糖尿病阿基塔小鼠治疗疗效的体内评估.

主要成果:

  • 通过在水中的胰岛素与D-PLA-PEG的立体复合,自发形成约400纳米纳米粒子.
  • 在实验室中持续释放胰岛素从立体复合纳米颗粒,长达14周.
  • 在17周的时间内,在糖尿病阿基塔小鼠中观察到血糖水平的显著降低和正常体重增加.

结论:

  • 胰岛素-D-PLA-PEG立体复合纳米颗粒为持续和延长胰岛素释放提供了一个有希望的平台.
  • 在水性介质中的立体复合方法扩大了用于制造和蛋白质治疗的受控输送系统的适用性.
  • 这种新型纳米配方在糖尿病的临床前模型中显示出显著的治疗效果.