Increased antitumor efficacy of ginsenoside Rh(2) via mixed micelles: in vivo and in vitro evaluation

The aim of this work is to apply Solutol(®) HS15 and TPGS to prepare self-assembled micelles loading with ginsenoside Rh(2) to increase the solubility of ginsenoside Rh(2), hence, improving the antitumor efficacy. Ginsenoside Rh(2)-mixed micelles (Rh(2)-M) were prepared by thin film dispersion method. The optimal Rh(2)-M was characterized by particle size, morphology, and drug encapsulation efficiency. The enhancement of in vivo anti-tumor efficacy of Rh(2)-M was evaluated by nude mice bearing tumor model. The solubility of Rh(2) in self-assembled micelles was increased approximately 150-folds compared to free Rh(2). In vitro results demonstrated that the particle size of Rh(2)-M is 74.72 ± 2.63 nm(PDI = 0.147 ± 0.15), and the morphology of Rh(2)-M is spherical or spheroid, and the EE% and LE% are 95.27 ± 1.26% and 7.68 ± 1.34%, respectively. The results of in vitro cell uptake and in vivo imaging showed that Rh(2)-M could not only increase the cell uptake of drugs, but also transport drug to tumor sites, prolonging the retention time. In vitro cytotoxicity and in vivo antitumor results showed that the anti-tumor effect of Rh(2) can be effectively improved by Rh(2)-M. Therefore, Solutol(®) HS15 and TPGS could be used to entrapping Rh(2) into micelles, enhancing solubility and antitumor efficacy.