Development of poly(hydroxyethyl methacrylate) nanogel for effective oral insulin delivery

Pharm Dev Technol. 2018 Apr;23(4):351-357. doi: 10.1080/10837450.2017.1295064. Epub 2017 Mar 3.

Abstract

Because of uncomfortable, painful and even deleterious effects of daily injection of insulin, extensive efforts are being made worldwide for developing noninvasive drug delivery systems, especially via the oral route. In this study, we synthesized hydroxyethyl methacrylate (HEMA) nanogel via emulsion polymerization method. The morphology and stability of the nanogel were characterized by scanning electronic microscope and dynamic light scattering. In vivo results showed the soft HEMA nanogel had longer half-live in the body circulation and exhibited almost negligible uptake by the macrophage cells as compared with blank cells. For the FITC-dextran tracking for intestinal penetration, the results indicated that the FITC-dextran in the soft nanogel penetrated faster from the inner side of the abdominal segment, which explained why the soft HEMA nanogel could promote intestinal absorption of encapsulated insulin. In vivo delivery of insulin encapsulated in the soft HEMA nanogel sustained blood glucose control for 12 h, and the overall bioavailability of administrated insulin was much higher than free insulin. Our results showed that the insulin-loaded HEMA nanogel was able to efficiently control blood glucose as a delivery system, suggesting the HEMA nanogel using emulsion polymerization could be an alternative carrier for oral insulin delivery.

Keywords: HEMA nanogel; diabetes; emulsion polymerization; insulin; oral delivery.

MeSH terms

  • Administration, Oral
  • Animals
  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy*
  • Drug Carriers / chemical synthesis
  • Drug Carriers / chemistry*
  • Drug Delivery Systems
  • Emulsions / chemical synthesis
  • Emulsions / chemistry
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hydrogels / chemical synthesis
  • Hydrogels / chemistry*
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / therapeutic use
  • Insulin / administration & dosage*
  • Insulin / pharmacokinetics
  • Insulin / therapeutic use
  • Male
  • Mice
  • Polyhydroxyethyl Methacrylate / chemical synthesis
  • Polyhydroxyethyl Methacrylate / chemistry*
  • Polymerization
  • RAW 264.7 Cells
  • Rats, Sprague-Dawley

Substances

  • Blood Glucose
  • Drug Carriers
  • Emulsions
  • Hydrogels
  • Hypoglycemic Agents
  • Insulin
  • Polyhydroxyethyl Methacrylate