title: A nanoparticulate drug-delivery system for 20(S)-protopanaxadiol: formulation, characterization, increased oral bioavailability and anti-tumor efficacy.
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 Cmaxand AUClastvalues 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 IC50value 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.
authors.affiliation: a Institute of Medicinal Plant Development , Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , PR China and.
authors.forename: Meihua
authors.initials: M
authors.lastname: Han
authors.affiliation: b School of Pharmacy , Heilongjiang University of Chinese Medicine , Harbin , PR China.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Ma
authors.affiliation: b School of Pharmacy , Heilongjiang University of Chinese Medicine , Harbin , PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.affiliation: b School of Pharmacy , Heilongjiang University of Chinese Medicine , Harbin , PR China.
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Li
authors.affiliation: a Institute of Medicinal Plant Development , Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , PR China and.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Guo
authors.affiliation: a Institute of Medicinal Plant Development , Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , PR China and.
authors.forename: Xiangtao
authors.initials: X
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D001682:Biological Availability; D016503:Drug Delivery Systems / Q000379:methods*; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D012502:Sapogenins / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D013535:Suspensions
chemical_list: D000970:Antineoplastic Agents; D012502:Sapogenins; D013535:Suspensions; C062916:protopanaxadiol
keywords: 20(S)-protopanaxadiol nanosuspensions; anti-tumor efficacy; bioavailability; characterization; preparation