Preparation, characterization, and anti-4T1-tumor efficacy of quercetin nanoparticles / 中草药

ABSTRACT

Objective In order to solve the problem of poor water solubility of quercetin, quercetin nanosuspensions (Q-NSps) with high drug loading and suitable for intravenous administration was prepared, and study its anti-tumor effect in vitro and in vivo. Methods Quercetin was made into nanoparticles (Q-NSps) via the method of anti-solvent precipitation combined with high-pressure homogenization using polyethylene glycol 1 000 vitamin E succinate (TPGS) as stabilizer. The particle size of the resultant nanoparticles was measured by dynamic light scattering and the morphology was observed by scanning electron microscopy. The drug loading and the in vitro drug release were measured using HPLC analysis. In the meantime, the lyoprotectants were screened, the storage stability, hemolysis, and the suitability for intravenous injection were also studied; The in vitro anti-tumor activity of quercetin and its nanoparticles were assessed in contrast using MTT assay and the in vivo anti-tumor therapeutic efficacy was investigated using 4T1 tumor bearing mice. Results Q-NSps had uniform size and spherical shape, the average particle size was 143.9 nm, the polydispersity index (PDI) was 0.231, and the Zeta potential was -22.6 mV. The drug loading content was (45.82 ± 1.73) %. Using 1% maltose as lyoprotectant, Q-NSps could be lyophilized and then reconstituted into nanoparticles of the similar size. Q-NSps were stable for 30 d at storage, showed no hemolysis, and were suitable to intravenous administration. The resultant nanosuspensions displayed a good sustained in vitro release, and the cumulative release reaching 82.86% at 144 h. Q-NSps showed significantly higher growth inhibition against 4T1, HeLa, and HepG2 cell lines. The in vivo study demonstrated that Q-NSps (45 mg/kg, iv) had the similar antitumor therapeutic efficacy as paclitaxel injections (56.78% vs 55.08%, P > 0.05). Conclusion The obtained Q-NSps had small particle size, good stability, and significantly improved anti-tumor effect of quercetin in vitro and in vivo, so Q-NSps are promising to be a antitumor drug for application in clinic.