ABSTRACT
Objective: To prepare a anti-drug-resistant hybrid nanosuspension of quercetin and hydroxycamptothecin by employing the anti-drug resistance property of quercetin. Methods: The ratio of quercetin to hydroxycamptothecin was optimized by in vitro cytotoxicity test. The hybrid nanosuspension of quercetin and hydroxycamptothecin was prepared by the microprecipitation-high pressure homogenization method, with polyethylene glycol-poly(benzyl aspartateic acid)as stabilizers. The particle size, potential, morphology, crystal form and stability of nanosuspensions were studied by the dynamic light scattering, transmission electron micros-copy, differential scanning calorimetry and X-ray powder diffraction. The hemolytic effect of nanosuspension was analyzed by the UV spectrophotometry. The in vitro dissolution of nanosuspensions was investigated by the paddle method. Results: The particle size and Zeta potential of nanosuspensions were(216.3±5.93)nm and(0.197±0.035)mV, respectively. The nanosuspension showed an irregular shape in the transmission electron microscope image. Compared with the two raw drugs, the crystal forms of quercetin and hydroxycamptothecin in nanosuspension was likely transformed in the state of nanosuspension. The nanosuspension showed a good storage and dilution stability, and had good blood compatibility. The dissolution test showed that nanosuspensions could significantly increase the dissolution rate of the two drugs(both P<0.05). Conclusion: The combination of quercetin and hydroxycamptothecin in a favored ratio selected by the present study could significantly improve the antitumor effect of hydroxycamptothecin. The prepared quercetin and hydroxycamptothecin hybrid nanosuspensions showed good pharmaceutical properties, which might be used for further studies on the synergistic and detoxifying effect of the hybrid nanosuspensions.
ABSTRACT
Objective: To prepare curcumin(Cur)micelles with D-α-tocopherol polyethylene glycol 1000 suc- cinate(TPGS)as carrier, so as to improve the water solubility and antitumor activity of curcumin. Methods: The prepa- ration method of Cur/TPGS micelles was investigated under the indication of particle size and drug loading of the micelles. The particle size of micelle and Zeta potential were used as evaluation indices to optimize the feed ratio of Cur/TPGS. The particle size and morphology of the micelles were characterized by the dynamic light scatter(DLS)method and transmis- sion electron microscopy(TEM). The in vitro antitumor activity of Cur and Cur/TPGS micelles was evaluated by the MTT method. Results: The Cur/TPGS micelle was manufactured by the dialysis method. The optimum feed ratio of Cur/TPGS was 1:10. The Cur/TPGS micelles showed a spherical shape, with the average particle size and Zeta potential of 54.4 nm and-12.1mV, respectively. The drug loading and the encapsulation efficiency were 7.35% and 81.3%, respectively. The Cur/TPGS micelles had a good stability and showed an in vitro antitumor activity better than Cur in the MTT test. Conclu- sion: A stable Cur/TPGS micelle was prepared using the dialysis method in the present study, which greatly improved the water solubility and in vitro antitumor efficacy of Cur.