Ursolic acid nanoparticles for oral delivery prepared by emulsion solvent evaporation method: characterization, in vitro evaluation of radical scavenging activity and bioavailability

With the purpose of improving the water solubility and oral bioavailability, ursolic acid nanoparticles (UANs) were prepared by the emulsion solvent evaporation method, and the nanosuspension was freeze-dried into powder. The optimal conditions for preparing nanoparticles were screened out using single-factor experiment. Take advantage of the optimal conditions, UA nanoemulsion had mean particle size (MPS) of 69.7 ± 15.6 nm and polydispersity index value (PI) of 0.005. The MPS of UA nanosuspension was gained at 100.2 ± 12.1 nm (PI = 0.005), after the organic solvent was removed by rotary evaporator. Finally, UANs possessing an MPS of 157.5 ± 28.0 nm (PI = 0.005) and zeta potential of 20.33 ± 1.67 mV were obtained after freeze-dried. UANs were investigated using SEM, XRD, DSC, TGA and further explored their equilibrium solubility, dissolution rate, solvent residue analysis, cellular antioxidant activity and oral bioavailability. All the results above showed that UA in UANs was in the amorphous state. The result of solubility test figured that the equilibrium solubility of UANs was 13.48 times in simulated gastric fluid (SGF), 11.79 times in simulated intestinal fluid (SIF) and 23.99 times in deionized water than raw UA. Accordingly, the dissolution rate of UANs in SGF and SIF had an apparent enhancement. The oral bioavailability of UANs increased 2.68 times than raw UA. UANs improved antioxidant activity toward cells compared with raw UA, and EC50 of UANs reduced 37.5 times than raw UA. The residual contents of trichloromethane and ethanol were separated up to the mustard of the ICH limit for class III and class II solvents. The results above indicated that UANs possesses a value of application on enhancement oral bioavailability.