A nanoparticulate drug-delivery system for 20(S)-protopanaxadiol: formulation, characterization, increased oral bioavailability and anti-tumor efficacy. (1st September 2016)

• Record Type: Journal Article
• Authors: Han, Meihua; Ma, Liqiang; Yu, Xin; Li, Zhitao; Guo, Yifei; Wang, Xiangtao
• Is Part Of: Drug delivery. Volume 23:Number 7(2016:Oct.)
• Page Start: 2410
• Page End: 2418
• Publication Date: 2016-09-01
• Subjects: 20(S)-protopanaxadiol nanosuspensions -- anti-tumor efficacy -- bioavailability -- characterization -- preparation; Drug delivery systems -- Periodicals; Drug targeting -- Periodicals; 615.05
• DOI: 10.3109/10717544.2014.997843
• Languages: English
• ISSNs: 1071-7544

Abstract

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 C max 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.