Preparation Of Curcumol Lipid Nanosuspension And Study Of Its Antitumor Activity

Curcumol,also known as curcumin,is a sesquiterpene monomer compound.It is an important component isolated from the volatile oil of Curcuma Curcuma.It has anti-tumor,antibacterial,antipyretic and analgesic effects,and improves immunity.Compared with other chemically synthesized drugs,curcumol has fewer adverse reactions,weaker toxic and side effects on the human body,is more suitable for long-term treatment,and has great prospects in the application of anti-tumor.However,curcumol is almost insoluble in water,resulting in poor bioavailability,making it difficult to apply in clinical treatment.In this experiment,the actual compound curcumol was used as the raw material,and the dosage form was studied to improve its water solubility and bioavailability.In the experiment,curcumol lipid nanosuspension was prepared by a combination of precipitation method and high-pressure homogenization method.The preparation method,dosage,stabilizer,drug-lipid ratio,shear time,homogenization pressure and the factors such as the number of homogenization were investigated,the process was optimized using the orthogonal design method,and the prescription and preparation method were determined: accurately weigh 50.0 mg of curcumol,2.0 mL of absolute ethanol solution to dissolve;weigh 25.0 mg of egg yolk Phospholipid,50.0 mg PVP and 50.0 mg poloxamer 188 were added to 80.0 mL of pure aqueous solution and stirred and dissolved at 0 ℃.Under stirring at a low temperature(0 ~3 ℃),2.0 mL of an absolute ethanol solution containing 50.0 mg curcumol was slowly injected into the aqueous phase.After the injection was completed,the resulting test solution was sheared at 2.0 × 104 r · min-1 for 3 minutes at high speed,and then subjected to microjet high pressure homogenization 3 times under the condition of 13.6 × 107 Pa,and rotary evaporation at 45 ℃ to remove trace ethanol,namely Curcumol lipid nanosuspension(Cur-LNS).Making curcumol into a lipid nanosuspension can improve solubility and increase bioavailability.In order to improve the storage stability of curcumol lipid nanosuspension,it needs to be prepared as Cur-LNS lyophilized powder.Through the investigation of different types and mass fractions of lyoprotectants,the final lyophilization process was determined according to various indicators such as appearance after lyophilization,ease of reconstitution,particle size and potential after reconstitution.For: add 10% mannitol per ml of curcumol lipid nanosuspension as a lyoprotectant.After dissolution,pre-freeze in a refrigerator at-80 ℃ for 24 h,and then put it in a freeze dryer for 8h Freeze-drying to obtain curcumol lipid nanosuspension lyophilized powder.Curcumol lipid nanosuspension lyophilized powder is loose and porous,and has good redispersibility.After being placed at room temperature for 6months,there is no obvious change in the appearance of the preparation.The physical and chemical properties of curcumol lipid nanosuspension lyophilized powder were investigated to determine its good stability.The experiment evaluated the pharmacological properties of Cur-LNS.The results are as follows: The particle size and Zeta-potential of Cur-LNS were measured.The average particle size was 313 nm and the average Zeta-potential was-23 m V.Observed by transmission electron microscope,curcumol lipid nanosuspension was spherical in shape,with uniform shell and core structure,and uniform distribution;from scanning electron microscope observation,Cur-LNS lyophilized powder was spherical,beautiful,uniform in size,and regularly distributed.The MTT method was used to conduct in vitro antitumor activity experiments on Hep G2,HEK293,HT29,and S180 cell lines.The results showed that curcumol lipid nanosuspension has a slow-release type and showed higher in vitro antitumor activity.S180 ascites tumor mice experiments show that Cur-LNS has a higher tumor suppressor index than curcumol,which has obvious anti-tumor effect.By orally administering to rats,a method for the detection of curcumol in plasma samples was established,and the pharmacokinetic behavior of curcumol lipid nanosuspension and curcumol bulk drug(Cur-S)in mice The research was carried out and the pharmacokinetic parameters were analyzed.According to the pharmacokinetic parameters,the AUC0-∞ of Cur-S is 238.73 μg / mL ? h,and the AUC0-∞ of Cur-LNS is 506.12 μg / mL ? h.The results show that the action time of Cur-LNS in rats Prolonged,with higher relative bioavailability and enhanced drug efficacy.The research results of this topic provide ideas for the development of insoluble anti-tumor drugs,and have very important significance for the clinical development and application of Cur.