We aimed to evaluate whether the enhancement of the liver accumulation and anti-inflammatory activity of dexamethasone acetate (DXMA) could be achieved by incorporating it into nanostructured lipid carrier (NLCs). DXMA-NLCs were prepared using a film dispersion-ultrasonication method and characterized in terms of particle size, PDI, zeta potential, differential scanning calorimetry, drug loading capacity, encapsulation efficiency, and in vitro release. The biodistribution and pharmacokinetics of DXMA-NLCs in mice were significantly different from those of the DXMA solution (DXMA-sol). The peak concentration of DXMA-NLCs was obtained half an hour after intravenous administration. More than 55.62% of the total administrated dose was present in the liver. An increase of 2.57 fold in the area under the curve was achieved when compared with that of DXMA-sol. DXMA-NLCs exhibited a significant anti-inflammatory and hepatoprotective effect on carrageenan-induced rats and carbon tetrachloride-induced mice compared with DXMA-sol. However, the effect was not in proportion to the dosage. The intermediate and low dosages presented better effects than DXMA-sol. All results indicate that NLCs, as a novel carrier for DXMA, has potential for the treatment of liver diseases, increasing the cure efficiency and decreasing the side effects on other tissues.
Keywords: dexamethasone acetate; liver targeting; nanostructured lipid carrier.