| Based on the superior characteristics of D-a-tocopherol polyethylene glycol 1000 succinate(TPGS),vitamin E succinate modified chitosan oligosaccharide(VES-g-CSO)and integrin targeted RGD peptides,VES-g-CSO and TPGS-RGD were synthesized and utilized in the preparation of paclitaxel-loaded VES-g-CSO/TPGS-RGD mixed micelles(PTX@VES-g-CSO/TPGS-RGD).The physiochemical properties as well as anti-tumor effects were further investigated.VES-g-CSO and TPGS-RGD were successfully synthesized and characterized by IR,1H-NMR and elemental analysis.The critical micelle concentration(CMC)of VES-g-CSO and VES-g-CSO/TPGS mixture were 50.2 ?g/mL and 20.1 ?g/mL,respectively.PTX@VES-g-CSO,PTX@VES-g-CSO/TPGS and PTX@VES-g-CSO/TPGS-RGD micelles were prepared by organic solvent emulsification-evaporation method.And exhibited uniform size(152.0?196.8 nm),positive zeta potential(+17.4?35.0 mV)and spherical morphology.When the mass ratio of PTX to carrier materials was 1:13,the loading efficiency of PTX@VES-g-CSO,PTX@VES-g-CSO/TPGS and PTX@VES-g-CSO/TPGS-RGD were 1.40%,6.07%and 5.94%,respectively.The in vitro release indicated that all the PTX-loaded micelles showed a burst release in the initial 30 min and followed by a sustained-release.Besides,the cumulative drug release of PTX@VES-g-CSO/TPGS-RGD was slightly higher than PTX@VES-g-CSO micelles.Cellular uptake of VES-g-CSO/TPGS-RGD in U87MG cells was found to be higher than other micelles.After being pre-treated with free RGD,the U87 MG cells uptake less VES-g-CSO/TPGS-RGD.In vitro cytotoxicity assay showed that,the IC50 of PTX@VES-g-CSO/TPGS-RGD(0.042±0.003?g/mL)against U87MG cells was significantly higher than Free PTX treatment(0.523±0.021 ?g/mL).Cellular apoptosis results showed the percentage of early and late apoptosis of U87MG cells in PTX@VES-g-CSO/TPGS-RGD treatment were 23.5%and 10.3%,respectively,which suggest that RGD-modified drug loaded mixed micelles induced apoptosis was significantly enhanced. |
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