| Quercetin(QUT)is a kind of flavonoid compounds widely existed in the nature.It has many effects such as anti-oxidation,anti-inflammatory and anti-tumor.However,the clinical application of QUT has been limited by its low water solubility.Hyaluronic acid(HA)is a polymer hydrophilic polysaccharide,featured with biodegradability,biocompatibility and non-immunogenicity.HA is a natural ligand of CD44 receptor on the surface of cancer cells.Therefore,the combination of QUT and HA is expected to improve the drawback of QUT.In this research,hyaluronic acid-based quercetin nano-formulations(QUT/HA-NFs)were prepared to improve the dissolution and selectivity of QUT.The content of this research mainly includes the following three parts:The first part was the preparation and evaluation of QUT/HA-NFs.Objective: To prepare QUT/HA-NFs and evaluate the physicochemical properties.Methods: QUT/HA-NFs were prepared by a modified grinding method,the particle size and zeta potential were detected by Malvern instrument,the morphology was observed by transmission electron microscopy,the crystal form of QUT/HA-NFs were investigated by differential scanning calorimeter,and the interaction of QUT and HA were evaluated by Fourier transform infrared spectroscopy.Moreover,the drug loading was measured by ultraviolet spectrophotometry,and the dynamic dialysis bag method was used to evaluate the in vitro release of QUT/HA-NFs.Results: QUT/HA-NFs were prepared,and its appearance was a yellowish suspension.The particle size and zeta potential were 235.9 ± 3.2 nm and-36.8 ± 0.9 mv,respectively.Transmission electron microscope observation illustrated that the morphology of QUT/HA-NFs was shuttle like or needle like.The drug loading was 13.8 ± 1.4%,the in vitro release of QUT/HA-NFs was 95.7 ± 3.1%,and the drug exists in an amorphous state.Conclusion: QUT/HA-NFs were successfully prepared,and the physicochemical parameters of QUT/HA-NFs were appropriate.The second part was cytological evaluation of QUT/HA-NFs.Objective: To evaluate the targeting cell inhibition of QUT/HA-NFs.Methods: The cell inhibition of QUT/HA-NFs on 4T1 and HepG2 cells were evaluated by MTT assay,the cellular uptake of QUT/HA-NFs were observed by a confocal laser scanning microscope.Flow cytometry was used to investigate the effect of QUT/HA-NFs on tumor cell apoptosis.Results: The cell inhibition rates of QUT/HA-NFs with different concentration were higher than those of QUT groups.The QUT/HA-NFs were taken up by 4T1 cells in a time-dependent manner,and the apoptosis rate of QUT/HA-NFs on 4T1 cells and HepG2 cells were 23.22% and 15.35%,respectively.Conclusion: QUT/HA-NFs have anti-tumor effects in vitro,and it could successfully effectively inhibit the growth of tumor cells.The third part was the preliminary evaluation of anti-tumor effects of QUT/HA-NFs in vivo.Objective: To evaluate the anti-tumor effects of QUT/HA-NFs in vivo.Methods: The xenograft tumor mice model was established,and the changes of tumor volume and body weight were recorded to evaluate the anti-tumor effects.Results: No abnormal changes in mice body weight were observed,and the tumor volume of QUT/HA-NFs group was significantly smaller than the other groups.Conclusion: Experimental data shows that QUT/HA-NFs have anti-tumor effects in vivo. |
PDF Full Text Request