Preparation, optimization, characterization and in vivo pharmacokinetic study of asiatic acid tromethamine salt-loaded solid lipid nanoparticles

Abstract

Purpose: To enhance the oral bioavailability of asiatic acid tromethamine salt (AAS) by encapsulation in solid lipid nanoparticles (SLN).Methods: The AAS-loaded SLN (AASLN) was prepared by the modified solvent injection method with glycerin monostearate (GMS) as lipid and poloxamer 188 as surfactant. A Box–Behnken design was used to optimize the formulations. Physicochemical characterization was carried out by using dynamic light scattering, scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Stabilities at 4 °C and pH 1.2 were investigated by particle size or/and entrapment efficiency (EE%). The in vivo pharmacokinetics was evaluated by HPLC-MS/MS.Results: The optimal formulation of AASLN had an average size of 237 nm with zeta potential of −35.9 mV, and EE% of 64.4%. SEM showed that the AASLN had spherical shape with smooth surface. Furthermore, DSC and X-ray analyses indicated that AAS was amorphous state and the crystal degree of GMS was significantly decreased in the formulation. AASLN showed excellent stability at 4 °C for 1 month and no coacervation at pH 1.2. The bioavailability of AAS in SLN was found to be 2.5-fold higher than that of AAS alone after a single oral administration in rats.Conclusions: This study reveals that SLN is developed as a promising oral delivery system of AAS with significantly enhanced bioavailability and good storage stability.