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Related Concept Videos

Insulin Formulations: Types and Delivery01:27

Insulin Formulations: Types and Delivery

202
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...
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Oral Hypoglycemic Agents: Glinides01:06

Oral Hypoglycemic Agents: Glinides

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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

Glucagon-like Receptor Agonists

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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

Insulin: Dosing Regimen and Adverse Effects

181
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.
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...
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Insulin Secretory Vesicles01:05

Insulin Secretory Vesicles

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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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Insulin Extended Release from PLA-PEG Stereocomplex Nanoparticles.

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
Summary

This study introduces a novel nano formulation for peptide and protein drugs using a stereocomplexation mechanism. The developed insulin nanoparticles demonstrate sustained release and effective therapeutic outcomes in diabetic mice.

Keywords:
PLA, PLA‐PEGcontrolled releasedrug deliveryinsulinpeptide drugstereocomplex

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Area of Science:

  • Biomaterials Science
  • Drug Delivery Systems
  • Nanotechnology

Background:

  • Peptide and protein therapeutics face challenges in stability and controlled delivery.
  • Existing drug delivery methods often struggle with the inherent instability of these biomolecules.
  • Developing effective delivery systems is crucial for therapeutic success.

Purpose of the Study:

  • To develop a novel nano formulation for controlled drug delivery of peptide and protein therapeutics.
  • To utilize a stereocomplexation mechanism in aqueous media for enhanced stability.
  • To evaluate the in vitro and in vivo performance of the developed system.

Main Methods:

  • Fabrication of nanoparticles using poly(D-lactide)-polyethylene glycol (D-PLA-PEG) and insulin in aqueous media via stereocomplexation.
  • Characterization of nanoparticle size (≈400 nm) and spontaneous formation due to concave-convex fitness.
  • In vitro release studies in phosphate buffer solution (PBS) at pH 7.4.
  • In vivo evaluation of therapeutic efficacy in diabetic Akita mice over 17 weeks.

Main Results:

  • Spontaneous formation of ≈400 nm nanoparticles through stereocomplexation of insulin with D-PLA-PEG in water.
  • Sustained in vitro release of insulin from the stereocomplex nanoparticles for up to 14 weeks.
  • Significant reduction in blood glucose levels and normal body weight gain observed in diabetic Akita mice over 17 weeks.

Conclusions:

  • Insulin-D-PLA-PEG stereocomplex nanoparticles offer a promising platform for sustained and extended insulin release.
  • The stereocomplexation approach in aqueous media broadens the applicability for fabricating controlled delivery systems for peptide and protein therapeutics.
  • This novel nano formulation demonstrates significant therapeutic efficacy in a preclinical model of diabetes.