Category: Formulation and Quality
Purpose: Oleanolic acid (OA) has anti-inflammatory and anti-cancer effects and is clinically used in the treatment of liver cirrhosis and liver injury. However, OA has low water-solubility, serious intestinal cephalic effect, and extremely low oral bioavailability. In the present research, we aimed to develop a formulation to improve the oral bioavailability of OA.
Methods: The OA-loaded solid lipid nanoparticles (SLN) composed of propylene glycol monolaurate glyceride and sodium oleate (OA-SO-SLN) was prepared via a melt-emulsifying method. OA-loaded SLN without sodium oleate was also studied as control. The particle size, zeta potential, morphology, viscosity, and in vitro drug dissolution characteristics of the prepared SLN were determined. In addition, the absorption characteristics of OA-SLN and OA-SO-SLN were investigated using a single-pass intestinal perfusion method in rats. Furthermore, pharmacokinetic studies of the prepared SLN were investigated.
Results: The mean particle size of OA-SO-SLN and OA-SLN was 166.31±6.07 nm (polydispersity index (PDI): 0.16±0.02) and 205.5±3.16 (PDI: 0.224±0.01), respectively. The zeta-potential of the prepared SLN was -45.65±3.88 mV and -24.71±1.11 for OA-SO-SLN and OA-SLN, respectively. The entrapment efficiency (EE) of both formulations was over 98.32 %. In addition, the morphology of the SLN appeared to be spherical and monodispersed (Figure 1). The viscosity of OA-SO-SLN and OA-SLN is 1180.54 mPa·s and 10.49±0.41 mPa·s, respectively. It was demonstrated that Papp and Ka values of OA-SO-SLN were higher than OA-SLN in the single-pass intestinal perfusion experiment (Figure 2).
Conclusion: OA-SA-SLN has excellent stability and biological adhesion characteristics, which could prolong the drug retention time in vivo, thus enhancing OA oral bioavailability.