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Abstract
As with many other hydrophobic anticancer agents, 20(S)-protopanaxadiol (PPD) has a very low oral bioavailability. In this study, a precipitation-combined ultrasonication technique was used to prepare PPD nanosuspensions. The mean particle size of the nanosuspensions was approximately 222 ± 12 nm, the drug payload achieved 50% after lyophilization and the maximum PPD concentration can reach 100 mg/ml, which is over 30 000 times the solubility of PPD in aqueous solution (3 μg/ml). After oral administration, the Cmax and AUClast values of PPD nanosuspensions were approximately 3.66-fold and 3.48-fold as those of PPD coarse suspensions, respectively. In contrast to the free drug solution, PPD nanosuspensions showed higher in vitro anti-tumor activity against HepG-2 cells (an IC50 value of 1.40 versus 5.83 μg/ml at 24 h, p < 0.01). The in vivo study in H22-tumor-bearing mice demonstrated that PPD nanosuspensions showed good anti-tumor efficacy with an inhibition rate of 79.47% at 100 mg/kg, while 50 mg/kg of cyclophosphamide was displayed as positive control, and the inhibition rate was 87.81%. Considering the highest drug payload, oral bioavailability reported so far, significant anti-tumor efficacy and excellent safety of encapsulated drugs, PPD nanosuspensions could be used in potential effective strategies for anticancer therapy; further investigation is ongoing.
Declaration of interest
The authors are thankful to the National Natural Science Foundation of China for financial support (Project no. 81102813), Open Project for Key Laboratory, Heilongjiang University of Traditional Chinese Medicine (2013kf05) and the National S&T Major Special Project on Major New Drug Innovation (2012ZX09301002-001). The authors report that there are no conflicts of interest.