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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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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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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: 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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Insulin: Biosynthesis, Chemistry, and Preparation01:25

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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.
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Injectable Gelled Multiple Emulsion for Glucose-Responsive Insulin Delivery.

Kofi Oti Boakye-Yiadom1,2, Qijing Chen1,2, Yilong Teng1,2

  • 1Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, 200240, China.

Advanced Healthcare Materials
|July 12, 2024
PubMed
Summary

This study presents a novel glucose-responsive insulin delivery system using a gelled multiple emulsion. This system effectively controls blood glucose levels in diabetic mice for extended periods.

Keywords:
PVPBA homopolymerdiabetesglucose‐responsiveinjectable gelled multiple emulsionsinsulin delivery

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Area of Science:

  • Biomaterials Science
  • Drug Delivery Systems
  • Diabetes Research

Background:

  • Insulin therapy for diabetes is limited by a narrow therapeutic window.
  • Developing glucose-responsive systems is crucial for sustained blood glucose control.

Purpose of the Study:

  • To develop a novel glucose-responsive insulin delivery system using a gelled multiple emulsion.
  • To evaluate its efficacy in a type 1 diabetic mouse model.

Main Methods:

  • Insulin was loaded into a water-in-oil-in-water (W1/O/W2) gelled multiple emulsion stabilized by poly(4-vinylphenylboronic acid) (PVPBA).
  • The system's encapsulation efficiency, stability, and injectability were assessed.
  • In vitro glucose-triggered insulin release was studied.
  • In vivo efficacy was evaluated in streptozotocin-induced type 1 diabetic mice.

Main Results:

  • The gelled emulsion achieved 99% encapsulation efficiency with enhanced stability and shear-thinning properties for easy injection.
  • The system demonstrated glucose-dependent insulin release under hyperglycemic conditions.
  • A single subcutaneous injection in diabetic mice showed a prolonged antihyperglycemic effect compared to free insulin.

Conclusions:

  • The developed gelled multiple emulsion serves as an effective glucose-responsive insulin delivery system.
  • This system offers sustained blood glucose equilibrium, addressing limitations of conventional insulin therapy.
  • The PVPBA-based emulsion shows promise for improved diabetes management.