Efficacy of a new delivery system based on solid lipid microparticles for the oral administration of the non-conventional antioxidant IAC on a diabetes mouse model

J Endocrinol Invest. 2018 Oct;41(10):1227-1236. doi: 10.1007/s40618-018-0858-4. Epub 2018 Mar 6.

Abstract

Purpose: We previously showed the positive effects of the new antioxidant molecule bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC) in reducing basal hyperglycaemia and relieving glucose intolerance in a diabetes model. However, the chemical properties of IAC did not allow an efficient oral administration, thus representing the main failing of that study. Here, we tested the effect of a new oral delivery system based on solid lipid microparticles (SLMs) in a diabetes mouse model.

Methods: The diabetes model was induced in C57B1/6J mice using streptozotocin and nicotinamide. Only the animals that overcame the glycaemic threshold of 180 mg/dL were enrolled in the study. Diabetic animals were then randomly assigned to 4 groups (n = 9) and treated once a day for 5 consecutive weeks with IAC (50, 100, and 150 mg/kg b.w.). The control group was composed of (n = 7) healthy mice that received only the vehicle. Glucose level was weekly monitored during the treatment period and up to 3 weeks after the suspension of the treatment. Glucose tolerance and insulin-resistance test were carried out.

Results: Our results showed that SLMs maintained the IAC effect in reducing basal hyperglycaemia as well as improving the insulin sensitivity and glucose tolerance.

Conclusion: The present study confirms that SLMs are promising drug carriers, which allow the oral administration of IAC ensuring its therapeutic efficacy. The concrete possibility to administer IAC per os represents a significant breakthrough in the putative consideration of this multi-radical scavenger in the diabetes therapeutic approach.

Keywords: Antioxidants; Diabetes; Mice; Oxidative stress; Solid lipid microparticles (SLMs).

MeSH terms

  • Administration, Oral
  • Animals
  • Antioxidants / administration & dosage*
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / blood*
  • Diabetes Mellitus, Experimental / drug therapy*
  • Drug Delivery Systems / methods*
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Lipids
  • Male
  • Mice
  • Microspheres*
  • Particle Size
  • Random Allocation
  • Treatment Outcome

Substances

  • Antioxidants
  • Blood Glucose
  • Hypoglycemic Agents
  • Lipids