In Silico Study of Phospholipids as An Oral Insulin Delivery System

Abstract

Phospholipids have been applied as a material for an oral insulin delivery system that either in the form of solid lipid nanoparticles, liposomes, or microemulsions. However, the administration of this delivery system for diabetic treatment requires twenty times higher of dosage than the injection one. In the present study, we performed molecular dynamics simulation to evaluate how phospholipids can protect insulin at the molecular level and why its efficiency for the diabetic treatment is low. Phosphatydilcholine group, such as DPPC, OPPC, LPC and combine of DPPC-LPC, was used as the phospholipid material to model the delivery system in our simulations because in vitro and in vivo studies of these phospholipids as the delivery system have been well-conducted. In these simulations, the waters-phospholipid-insulin system was prepared by randomly mixing phospholipids molecules inside the solvent box containing an insulin molecule. NPT ensemble was used in all simulations with the setting temperature at 310 K and 1 atm for the pressure. The simulation results showed that DPPC and LPC delivery systems were able to maintain both secondary and tertiary structures of the encapsulated insulin within the time range of simulation. However, all phospholipid delivery system models failed to fully encapsulate insulin surface within 150 ns simulation. This study may explain the reason for the low success rate of using phospholipid as the delivery system of oral insulin in the experiment.