Rhaponticin (RA) extracted from many medicinal plants has been demonstrated to possess a variety of pharmacological activities including potent antitumor, antitumor-promoting, antithrombotic,
antioxidant and
vasorelaxant activities. However, its poor solubility and bioavailability restricted the clinical application greatly. In this work, surface modification of
liposome with
polyethylene glycol (PEG) was developed with the purpose of improving the pharmacokinetics and anti-
tumor efficacy of RA. PEGylated liposomal RA (
PEGL-RA) was prepared by dry-film method. Its mean particle size was 89.3 +/- 8.7 nm, mean zeta potential was -4.1 mV and encapsulation efficiency was 67.4 +/- 6.4%. Moreover, the results of pharmacokinetic analysis showed that the time of maximum plasma concentration (Tmax) of
PEGL-RA was about 4.5 times higher than that of free RA after
oral administration due to the lower distribution into the gastrointestinal tract. The mean T1/2 value of
PEGL-RA and free RA were 350.12 +/- 0.87 min and 180.02 +/- 1.96 min, respectively. The AUC0-->infinity ratio of
PEGL-RA to free RA was about 2.41-fold (93.23 microg/mLmin/40.81 microg/mLmin).
Plasma protein binding ability of RA was also studied. The results showed that RA with 33.6 microg/mL concentrations in human plasma and HSA achieved the percent of bound 39.23 +/- 3.78% and 22.28 +/- 2.34%, respectively. In the in vivo studies utilizing solid
tumor-bearing rat, it was confirmed that
PEGL-RA delivered remarkably larger amount of RA to
tumor tissue and provided more significant anti-
tumor activity than free RA. Furthermore, the cytotoxicity and fluorescence microscopic studies showed higher intracellular uptake of
PEGL-RA than that of RA. In conclusion, PEGylated
liposome was an effective delivery formulation for RA to increase the pharmacokinetics and therapeutic efficacy.