| Curcumin?CUR?is an effective chemical component extracted from the roots of Zingiberaceae plants or Araceae plants,and it is safe to use due to its non-toxic side effects.CUR has broad application prospects due to its plenty of pharmacological activities including hypolipidemic,anti-inflammatory,antioxidant,antibacterial and choleretic properties,antitumor and other pharmacological effects and biological activities.However,its further clinical application is severely limited due to the low water solubility of CUR.Therefore,in this study,in order to improve the solubility of CUR in water and expand pharmaceutical application of CUR,curcumin/dimethyl-?-cyclodextrin inclusion complex?CUR-DM-?-CD IC?was prepared by ultrasonic microwave-freeze drying method,using dimethyl-?-cyclodextrin?DM-?-CD?as the inclusion material.After then,the preparation process was optimized by investigating the effect of the inclusion temperature,inclusion molar ratio,inclusion time and ultrasonic power on the preparation process,in which the encapsulation efficiency was used as the index of evaluation.Then the phase solubility study was performed to study the effect of different concentrations of DM-?-CD on the water solubility of CUR,and inclusion thermodynamics was also investigated.Moreover,CUR-DM-?-CD IC was further confirmed by the infrared spectroscopy?FT-IR?,differential scanning calorimetry?DSC?,X-ray diffraction?P-XRD?,scanning electron microscopy?SEM?.Finally,the physicochemical properties,such as dissolution,stability,antioxidant activity,antibacterial activity and permeability,were further determined,evaluating the effect of CUR-DM-?-CD IC on the physicochemical and pharmaceutical properties of CUR.?1?In the preparation section of CUR-DM-?-CD IC.First,the analysis method was established to determine the concentration of CUR and CUR-DM-?-CD IC in ethanol solution by high performance liquid chromatography?HPLC?.The concentration of CUR at a concentration range from 15?g/mL to 75?g/mL was determined by HPLC in ethanol solution.It has a good linear relationship between the concentration of CUR?X?and the peak area?Y?.The linear regression equation was Y=14.552X-19.452,R2=0.9998.The method validation experiment shows that the analysis method is simple and accurate,which can be used as an analysis method for subsequent experiments.Then the phase solubility studies showed that the phase solubility diagram of CUR in DM-?-CD aqueous solution showed a linear increase when the concentration of DM-?-CD was in the range of 0-15 mM,phase solubility diagram can be classified as AL type,indicating the molar ratio was 1:1 between DM-?-CD and CUR.At the same time,it was found that the reaction system of CUR and DM-?-CD was a spontaneous and endothermic process by inclusion thermodynamics,the formation of inclusion complex can be promoted by appropriately improving the reaction temperature.Finally,the effect of inclusion temperature,inclusion molar ratio,inclusion time and ultrasonic power on the preparation process of CUR-DM-?-CD IC was investigated by response surface method to optimize the preparation process of CUR-DM-?-CD IC.And the experiment results showed that the best inclusion process was:ultrasonic wave power was 150W,the inclusion temperature was 45°C,the inclusion time was 45 min,and the molar ratio was 1:1.?2?In the characterization of the inclusion complex,the formation of CUR-DM-?-CD IC was verified by infrared spectroscopy,differential scanning calorimetry,powder X-ray diffraction,scanning electron microscopy.It is shown that CUR was successfully wrapped into the cavity of DM-?-CD under the optimal process inclusion condition.After then,the quality of CUR-DM-?-CD IC was investigated by stability test.Finally,the solubility test and dissolution test were performed to study the effect of inclusion complex on the solubility and dissolution of CUR in water.The experimental results show that CUR-DM-?-CD IC is stable to light and heat,and the content was changed in a high-humidity environment,indicating CUR should be stored in the good-dry environment,and the solubility and dissolution rate of the CUR was also enhanced by inclusion technology.?3?In the research part of the antioxidant,antibacterial,and transdermal activity of the inclusion complex.a)The effects of different concentrations of CUR and CUR-DM-?-CD IC on DPPH free radicals,superoxide anion?O2-?radicals,hydroxyl?OH?radicals and ABTs+radical scavenging rates were investigated.The results showed that CUR-DM-?-CD IC has a higher clearance rate for DPPH free radicals,OH radicals and ABTs+radicals than CUR.However,the CUR-DM-?-CD IC had no significant change in the scavenging rate of superoxide anion radicals compared to CUR.b)In the experimental part of the antibacterial activity and antitumor activity of the inclusion complex.In the antibacterial activity part,Escherichia coli and Staphylococcus aureus were used as representative bacteria of G-and G+respectively,and the antibacterial activity of CUR and CUR-DM-?-CD IC was investigated.The experimental results showed that the antibacterial effect of CUR-DM-?-CD IC is significantly enhanced compared to raw CUR,indicating that the improvement of the solubility and dissolution rate is beneficial to increase the antibacterial activity of CUR.c)In addition,transdermal experiments showed that the cumulative permeabilities of CUR-DM-?-CD IC and CUR at 12 h were 121.75?g·cm-22 and 36.43?g·cm-22 respectively,indicating the transdermal rate of CUR was improved after the formation of the inclusion complex,and it can be said that the inclusion complex is a potential strategy to further exert the pharmacological properties of CUR. |
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