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.

Keywords:

• Asiatic acid tromethamine salt
• enhanced oral bioavailability
• modified solvent injection
• stable SLN

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.

Funding information

This study was supported by National Basic Research Program of China (973 Program, No.2013CB932504).