New glucose oxidase-immobilized stimuli-responsive dextran nanoparticles for insulin delivery

Int J Biol Macromol. 2019 Feb 15:123:968-978. doi: 10.1016/j.ijbiomac.2018.11.147. Epub 2018 Nov 16.

Abstract

Designing strategies for the use of biopolymer-based nanoparticles as drug delivery carriers is a considerable challenge in pharmaceutical science. Present study reports synthesis of a novel glucose responsive and in-vitro pH triggered insulin delivery system comprised of glucose oxidase immobilized on acryloyl crosslinked dextran dialdehyde (ACDD) nanoparticles. Scanning electron microscopy, transmission electron microscopy and particle size analysis data revealed that these carriers possess nanosize which is an important parameter for drug delivery applications. In-vitro insulin release studies were performed under artificial gastric fluid (AGF, pH 1.2) and artificial intestinal fluid conditions (AIF, pH 7.4) at physiological temperature (37 °C). Insulin release profile showed controlled release of about 70% under AIF conditions for 24 h. Insulin release mechanism studied using different kinetic models revealed that Korsmeyer-Peppas model appropriately explained the mechanism as 'non-Fickian' diffusion release of insulin. These glucose responsive stimuli sensitive nanocarriers exhibited controlled release of about 90% under AIF conditions in the presence of glucose. These findings revealed that these nanoparticles are promising and reliable delivery systems to overcome problems related with subcutaneous insulin therapy.

Keywords: Acryloylation; Glucose responsiveness; Insulin release.

MeSH terms

  • Carbon-13 Magnetic Resonance Spectroscopy
  • Dextrans / chemical synthesis
  • Dextrans / chemistry*
  • Drug Delivery Systems*
  • Drug Liberation
  • Enzymes, Immobilized / metabolism*
  • Glucose / metabolism
  • Glucose Oxidase / metabolism*
  • Humans
  • Hydrogen-Ion Concentration
  • Insulin / administration & dosage*
  • Kinetics
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Particle Size
  • Spectroscopy, Fourier Transform Infrared
  • X-Ray Diffraction

Substances

  • Dextrans
  • Enzymes, Immobilized
  • Insulin
  • Glucose Oxidase
  • Glucose