Preparation and pharmaceutical properties of an anti-drug resistant quercetin and hydroxycamptothecin hybrid nanosuspension / 国际药学研究杂志

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.