Self-assembling structures to treat diabetes
doi:10.1038/nindia.2018.159 Published online 5 December 2018
Scientists from the Birla Institute of Technology and Science, Pilani have developed a method by which lisofylline, a molecule with anti-diabetic properties, self-assembles into structures that protect β cells of the pancreas from cell death1. It also improves insulin production, providing a novel method to treat type-1 diabetes.
Type-1 diabetes is an auto-immune disease in which the insulin-producing β cells of the pancreas are killed. Lisofylline suppresses pro-inflammatory cytokines, protecting β cells from death. It also preserves insulin secretion.
Although this molecule has significant clinical potential, its applications have been limited as it has a very short half-life and is rapidly metabolised to pentoxifylline (PTX). Thus, to have any effect, it needs to be administered in very high doses – 25mg/kg twice daily.
This conversion to PTX has been attributed to a secondary hydroxyl group in the side chain of lisofylline. In a novel approach, the researchers protected this hydroxyl group by conjugating lisofylline to a fatty acid (linoleic acid). As lisofylline is hydrophilic and linoleic acid is hydrophobic, this conjugated structure self-assembles into lipid spheres called micelles.
The formation of micelles increased the half-life of lisofylline by 5.7 times, compared with free lisofylline, and also reduced its clearance. Tested in type 1 diabetic mice, free lisofylline could reduce, but not maintain the low glucose levels. However, in mice injected with lisofylline-conjugated structures, this reduction in glucose was stable and comparable to normal levels.
Additionally, these mice showed reduced inflammatory cytokines, increased insulin production and reduced death of islet β pancreatic cells.
This method thus opens new avenues for treating type-1 diabetes or other auto-immune diseases.
1. Mittal, A et al. Self-assembling lisofylline-fatty acid conjugate for effective treatment of diabetes mellitus. Nanomed-Nanotechnol. (2019) doi: 10.1016/j.nano.2018.09.014