Study On Preparation And In Vitro And In Vivo Evalution Of Curcumin Micelle

Since the reform and opening up,earth-shaking changes have taken place in our country,and the quality of life of the people has also reached an unprecedented level.At the same time,people are faced with practical issues such as climate warming,environmental pollution,fast pace of life,stress of work and so on,and suffer from a variety of cancers caused by these issues.At present,chemotherapy is the predominant treatment means of malignant tumor in clinic,and it is widely used in different stages of cancer occurrence.Chemotherapy has shown a good therapeutic effect in clinic,but it is also seriously limited because most drugs have some disadvantages,such as poor water solubility,low bioavailability,high side effects and so on.And,multidrug resistant(MDR)of tumor cells to chemotherapeutic drugs is also the common and thorny problem in clinic,which may lead to the failure of most chemotherapy.Curcumin is a polyphenolic compound extracted from turmeric,a traditional Chinese medicine.It is found to be a multi-target natural tumor preventive and therapeutic agent,but the use of curcumin is limited because it is insoluble in water and low bioavailability.Therefore,it is necessary to develop new dosage forms to meet the clinical application.As we all know,nano-drugs have absolute advantages in improving drug properties because of their special size effect and physical and chemical properties.By changing the pharmacokinetics and biological distribution of drugs in vivo to improve drug targeting,increase drug concentration in tumor cells and reduce systemic toxicity,it can help overcome the disadvantages of traditional drug preparations in terms of solubility,stability,side effects and bioavailability.In order to achieve the purpose of improving the efficacy of drugs,at the same time,nano-drugs can also reverse tumor multidrug resistance to a certain extent.in this study,curcumin was made into nano-micelles to improve the bioavailability of drugs,so as to give full play to its role in anti-tumor therapy.In this paper,polyglycol monomethyl ether-deoxycholic acid polymer material(mPEG-DCA)with good biocompatibility and anti-tumor multidrug resistance was used to encapsulate curcumin(Cur)with high efficacy and low toxicity.A new type of anti-resistant polymer micelle Cur / mPEG-DCA was successfully prepared by dialysis.The particle size,polydispersity coefficient(PDI),Zeta potential,etc.were characterized by a particle size analyzer,and the morphology of the polymer micelles was observed by a transmission electron microscope(TEM).The results show that under the optimal ratio conditions,the particle size distribution of the polymer micelles is good,with a spherical shape,the particle size is about49.31 nm,the PDI is about 0.277,the zeta potential is-10 ± 0.43 m V,and the drug loading is The encapsulation rate was 4.2% and 88.2%.In this paper,the dilution stability,storage stability,lyophilized powder reconstituted stability,and plasma stability of the micelle Cur / mPEG-DCA were also tested.The results show that the micelle Cur/mPEG-DCA has good stability.The hemolysis rate of Cur/mPEG-DCA was less than 5%,which indicated its biological safety was good.The release experiment results showed the micelle Cur/mPEG-DCA had a sustained-release performance.In conclusions,the above experimental results implied the further research Cur/mPEG-DCA micelle is of great significance.Then,the MTT method was used to investigate the inhibitory effect of polymer micelles Cur /mPEG-DCA on human lung cancer cells(A549)and human lung cancer cell resistant strains(A549 / PTX).The results showed that polymer micelles Cur / mPEG-DCA had a good inhibitory effect on human lung cancer cells(A549)and human lung cancer cell resistant strains(A549 / PTX)cells at 24 h and 48h;compared to curcumin Solution,the IC50 of Cur / mPEG-DCA micelles on human lung cancer cell resistant strains(A549 / PTX)cells is small,indicating that this micelle can reverse the drug resistance of tumor cells,so as to play a better role Antitumor activity of Cur / mPEG-DCA micelles.At last,the H22 tumor-bearing mice were employed as an experimental animal model in this paper,and the antitumor activity in vivo of Cur/mPEG-DCA and Cur solution were investigated by observing tumor volume in these mice.Animal survival and body weight were also monitored every day to preliminarily study systemic toxicity of the two formulations.Compared with normal saline group,the volume changes of tumor in Cur/mPEG-DCA and Cur solution are smaller(P<0.01),which indicates two formulation containing drug have significant effects on inhibiting the growth of the tumor.While the effect of Cur/mPEG-DCA is stronger than that of Cur solution.The results of the tumor volume inhibition rate also prove that the killing tumor ability of Cur/mPEG-DCA is stronger than that of Cur solution.According to on body weight data of the mice,it is found that the weight increase of mice in the saline group is significant during the experimental period,which may be attributed to the excessive growth of tumor and normal weight gain of the mouse.The mice in Cur/mPEG-DCA and Cur solution groups had almost noweight gain,which may be attributed to the inhibition effects on tumor growth or systemic toxicity.However,the animal survival number in Cur/mPEG-DCA group at 14 th day is significantly larger than that in Cur solution group,which means the systemic toxicity of Cur/mPEG-DCA maybe less than that of Cur solution.In conclusion,Cur/mPEG-DCA micelles in this paper can be used as potential delivery systems of Curcumin because of their good pharmaceutical properties,good antitumor activities in vitro and vivo,and possibly low systemic toxicity.The micelles in this paper will provide a new and feasible choice for the preparation of Curcumin-loaded polymer micelles.