Preparation And Properties Of Water-soluble Resveratrol

Resveratrol(Res)is known as a natural green anticancer drug after paclitaxel,which has anti-cancer,anti-inflammatory,and antilipidemic pharmacological effects.However,application of resveratrol is limited due to poor water solubility and low oral availability.Therefore,improvement of the water solubility and bioavailability for resveratrol is an important issue during the processing and utilization of resveratrol.The preparation process of water-soluble resveratrol by spray drying and self-microemulsion technology was optimized,and their structures were characterized.In addition,the in vitro antioxidant activity and anticancer activity of water-soluble resveratrol were measured,and the cytotoxicity of Res Self-microemulsion(Res SMEDDS)was examined.This work can be provide theoretical basis and technical support for development of water-soluble resveratrol.the main results are listed as followings:(1)The process of Res/Hydroxypropyl beta-cyclodextrin(HP-?-CD)inclusion complex prepared by spray drying method was optimized by orthogonal test the drug loading and solubility are 15.18%and 12.75 g/L respectively under optimal conditions of wRes:wHP-?-CD is 1:5(g/g),the stirring temperature is 30?,the feed flow rate is 2.1 mL/min,and the inlet air temperature is 140?.The condition was downloaded at a dose of 15.18%and the solubility was 12.75 g/L.Its in vitro dissolution at 5min increased from about 5%of the drug substance to more than 80%,and the dissolution is not affected by the pH of the dissolution medium,the antioxidant activity in vitro has not changed.At the same time,the structure of Res/HP-?-CD inclusion complex was characterized by UV,TEM and IR,and the formation of inclusion complex was confirmed.(2)The formulation of Res SMEDDS optimized by solubility experiment,compatibility experiment,pseudo ternary phase diagram and ternary phase diagram is:15%(w/w)isopropyl myristate(IPM),65%(w/w)cremophor RH40 and 20%(w/w)PEG400,and the amount of loading Res in Res SMEDDS is 5%.The average droplet size after emulsification from microemulsion is 28.0011.67nm,and its dissolution in vitro is increased from about 10%of the original drug to over 80%at 10min,and the dissolution is not affected by the pH of the dissolution medium.Stability experiments show that the stability of Res SMEDDS is good.(3)Cytotoxicity experiments showed that Res SMEDDS at a concentration of less than 100?M was safe.There was no significant difference in the DPPH+·and ABTS·free radical scavenging rates between the Res SMEDDS and Res powder.But Res SMEDDS has good in vitro anticancer activity in the concentration range of 0-100 ?M,and is better combined with 40 ?M 5-FU.