Synthesis Of Curcumin-Vitamin E Derivative And Its Nanoemulsions Anti-tumor Evaluation

Objective:In this study,we perform the chemical structure modification of curcumin?curcumin,CUR?in order to improve the dissolution of CUR and establish CUR-VE nanoemulusion formula with high encapsulation efficacy,good stability and significant antitumor activity.Methods:Curcumin—vitamin E?CUR-VE?derivatives was obtained by the reaction of CUR and D--tocopherol succinate under the cold bath with the 4-dimethylamino-pyridine?DMAP?and N,N'-dicyclohexylcarbodiimide?DCC?as catalyst and dehydrating agent,respectively.Silica gel column chromatography method was used to separate and purify the production by petroleum ether:ethyl acetate?4:1,3:1,2:1?as eluent.HPLC,H-NMR spectroscopy and mass spectrum were apllied to determine the purity and confirm the structure of CUR-VE.Cell proliferation inhibition activities of CUR and CUR-VE were carried out by MTT tests.The appropriate surfactant,amount of surfactant,ultrasonic time,ultrasonic power were selected according to the particle size and polydispersity.Establish the CUR-VE nanoemulusion by optimal process conditions.The configuration was measured by TEM and the particle size and polydispersity was measured by LPSA.Evaluate the in vitro release behavior by in vitro dissolution tester,the envelopment rate was evaluated by ultra-high speed centrifugation.HepG 2 cell proliferation inhibition activities of CUR,CUR-VE and CUR-VE nanoemulsions were carried out by MTT tests.Fluorescent inverted microscope was used to measure the cellular uptake of CUR,CUR-VE and CUR-VE nanoemulsions.Results:The structure of CUR-VE was confirmed by H-NMR spectroscopy and mass spectrum.The purity of CUR-VE isolated from silica gel column chromatography was more than 99.6%.The optimized nanoemulsion was as follows:VE as Oil phase,OP50 as surfactant.The content of OP50 was 55%to VE,probe ultrasonic conditions as follows:power is 60%of the total power,ultrasonic 3 seconds for 3 seconds,total ultrasonic time for 3 min.The CUR-VE nanoemulsion droplet?0/W?was sphercial and the particle size is around 100nm.Stability test results show that CUR-VE nanoemulsion remained transparent and clear after 4000 r/min,20min centrifugal.In vitro release experiment results show that CUR-VE nanoemulsion in neutral medium cumulative release of 59%.The MTT tests showed that HepG-2 IC50 of CUR,CUR-VE and CUR-VE nanoenulsion within 72 h were 28.384mmol/L,32.985mmol/L and 13.423mmol/L.Caco-2 IC50 of CUR,CUR-VE and CUR-VE nanoenulsion within 72 h were 17.4245mmol/L₂3.7726mmol/L.10.5062mmol/L?Prespectivety,CUR-VE nanoenulsion was superior to CUR and CUR-VE in rems of in-viro anti-cancer activity,and there was significant difference?P ? 0.05?.Fluorescent inverted microscope experiments show that cellular uptake of CUR-VE nanoemulsion was higher than CUR-VE and CUR.Concusion:Successfully synthesis of CUR-VE derivative,preparation of nano emulsion with good stability and has the stronger anti-cancer activity.