Enhanced oral bioavailability of ursolic acid nanoparticles via antisolvent precipitation with TPGS1000 as a stabilizer

Abstract

Ursolic acid (UA) has a wide spectrum of pharmacological activities. It is, however, extremely hydrophobic with poor oral bioavailability. To enhance its oral bioavailability, UA nanoparticles were prepared via antisolvent precipitation, using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS1000) as a stabilizer. Optimal TPGS1000/UA ratio of 0.4:1 was obtained, which produced the nanosuspension with 127 nm sized particles, the PDI of 0.15 and the ζ-potential of −24.4 mV. Differential scanning calorimetry and X-ray diffraction showed that the crystallinity of the UA within the nanoparticles was reduced by 94.1% in comparison to raw UA. This led to a significant increase in the dissolution rate in 0.1 M phosphate buffer solution (pH 6.8). Freeze-drying the UA suspension in the presence of trehalose did not affect properties of the particles, and the freeze-dried UA powder was a white fluffy powder with easy dispersion property. When administered orally to rats, the bioavailability and Cmax of the UA nanosuspensions were about 27.5-fold and 9-fold higher than those of raw UA, respectively. Our experiments proved that the UA nanoparticles with TPGS1000 as stabilizer could enhance absorption.