DMPK studies in rat model for comparative evaluation of bioavailability of alpha-mangostin and its formulated solid lipid nanoparticle using a validated LC-MS/MS method

Abstract

Garcinia mangostana L., contains the xanthone ?-mangostin, which is a bioactive secondary metabolite. The Caco-2 cell line transport of ?-mangostin was explored to see whether it could be used to study oral uptake. There has been little in-vivo research on the drug metabolism and pharmacokinetics of solid lipid nanoparticles of ?-mangostin. The ?-mangostin content estimation in plasma of rat was accomplished using a validated LC-MS/MS technique. The Papp (permeability coefficient apparent) across the Caco-2 cell monolayer is used to predict the absorption of orally administered ?-mangostin and ?-mangostin solid lipid nanoparticles (AM-SLNP). In the presence of the solid lipid and emulsifiers, AM-SLNP had 3.72 times higher Papp than ?-mangostin after 4 hours of study across the Caco-2 cell line. In-vivo rat model study show that formulated AM-SLNP has a 3.3-fold higher bioavailability than pure ?-mangostin. High tissue distribution of the AM-SLNP is observed compared to ?-mangostin, which may improve the efficacy of the product when compared to pure extract, as the available drug at the site of distribution is high. Because both cell monolayer and animal studies demonstrate the same pattern of drug intake mechanism for SLNP’s and as it is almost identical, nanotechnology can be utilized in avoiding hepatic metabolism and improving bioavailability.