Solid lipid nanoparticles (SLN) of Efavirenz as lymph targeting drug delivery system: Elucidation of mechanism of uptake using chylomicron flow blocking approach

Abstract

The aim of the present work was to develop a lymph targeted SLN formulation of antiretroviral (ARV) drug and to have an understanding of its underlying mechanism of uptake by the lymphatics. The lymphatics are the inaccessible reservoirs of HIV in human body. Efavirenz (EFV) is a BCS class II, ARV drug that undergoes extensive first pass metabolism. The EFV SLN formulation was prepared using Gelucire 44/14, Compritol 888 ATO, Lipoid S 75 and Poloxamer 188 by hot homogenization technique followed by ultrasonication method, with mean particle size of 168nm, polydispersity index (PDI) <0.220, and mean zeta potential of −35.55mV. DSC and XRPD studies revealed change in crystallinity index of drug when incorporated into SLN. In vitro drug release was found to be prolonged and biphasic in PBS pH 6.8. There was no significant change in the mean particle size, PDI, zeta potential and entrapment efficiency of EFV SLN after storage at 30±2°C/60±5%RH for two months. The results from lymphatic transport and tissue distribution study indicate that a significant part of the EFV had by-passed portal system and was recovered in the lymph via chylomicron uptake mechanism. Reduction in the amount (44.70%) of the EFV reaching to liver indicates that major amount of EFV bypasses the liver and thereby, enhances the oral bioavailability of the EFV. A significant amount of EFV was found in spleen, a major lymphatic organ. EFV SLN seems to have potential to target the ARV to lymphatics for the better management of HIV.