Objective: Eupatilin (EUP), as a natural flavone with various pharmacological properties, has a very low solubility in water. Nanoparticles have been widely used to increase the dissolution rate of drugs. This study aimed to assess the effect of nano-formulation of EUP in the form of EUP-loaded chitosan nanoparticles (EUP-NPs) on its solubility and to investigate its antihyperlipidemic potential in a model of hyperlipidemia induced by dexamethasone (DEX).
Materials and Methods: EUP-NPs were prepared using an ionotropic gelation procedure and their physicochemical properties were characterized. For induction of hyperlipidemia, DEX (10 mg/kg/day for 7 days) was injected subcutaneously in Wistar rats. Animals were randomized into seven groups, including: normal control, hyperlipidemic control, and hyperlipidemic rats which received EUP or EUP-NPs (50 and 100 mg/kg) or atorvastatin (40 mg/kg) as the reference group.
Results: EUP-NPs were entrapped effectively with a desirable particle size, polydispersity index (PDI) value, and controlled drug release. Saturated solubility test showed that the water solubility of EUP-NPs was increased about ten times compared to the free EUP. DEX led to a significant increase in serum lipid profile markers, atherogenic indices, lipid peroxidation, and liver enzymes activities. EUP-NPs (100 mg/kg) reduced the serum level of total cholesterol (20.55%, p<0.01), triglycerides (47.02%, p<0.01), low-density lipoproteins (28.69%, p<0.05), atherogenic indices (66.67%, p<0.001), malondialdehyde (p<0.01) and liver enzymes (p<0.05), and improved liver histopathologic abnormalities as compared to DEX hyperlipidemic group more effectively than free EUP.
Conclusion: This study revealed the higher water solubility for EUP-NPs, and more effective anti-hyperlipidemic and antioxidant activities in DEX-induced hyperlipidemia compared to free EUP.