Preparation And Antitumor Research Of Artesunate Nanoparticles Based On Hyaluronic Acid

Artesunate(ART)is a derivative component of artemisinin independently developed in my country.Compared with artemisinin,Compared with artemisinin,it is convenient to take,has various dosage forms and has higher potency than artemisinin.After oral administration,it can produce dihydroartemisinin in the body and then exhibit a certain pharmacological effect,play a highly effective antimalarial effect,and less toxic.In recent years,artesunate has shown good anti-tumor activity,low toxic and side effects,and has attracted widespread attention from pharmaceutical researchers at home and abroad.However,due to its poor water solubility,and its obvious first-pass effect and liver drug enzyme induction,it leads to low bioavailability,which limits its clinical application.In the research of this subject,we used hyaluronic acid(HA),a high molecular material with good biocompatibility and biodegradability,as a drug carrier,then prepared and characterized HA-ART nanoparticles by chemical reaction.Then,through a series of in vitro cell experiments,the inhibitory effect and mechanism of HA-ART on breast cancer cells were investigated.The results show that the artesunate nano drug-loading system can not only increase the solubility of ART in the aqueous solution and prolong the half-life of the drug,but also improve the bioavailability and increase the toxic effect of the drug on cancer cells.The hyaluronic acid-artesunate self-assembled nanoparticles(HA-ART)designed in this project are mainly prepared by the following method: by reacting artesunate with hyaluronic acid modified with adipic acid dihydrazide HA-ART conjugate;dissolve the prepared HA-ART conjugate in an appropriate amount in distilled water,stir and ultrasonically dissolve at room temperature to make it evenly dispersed in water,and self-assemble to form hydrophilic HA-ART nanoparticles.The structure was characterized by nuclear magnetic resonance hydrogen spectroscopy and infrared spectroscopy,which confirmed the synthesis of the target product.The particle size,potential and morphology of HA-ART nanoparticles were investigated using a laser particle size analyzer,a potential analyzer,and a transmission electron microscope.The results showed that the average particle size of the nanoparticles was 171.6 nm,the interface potential was-16.1 mv,and the PDI was 0.199,indicating HA-ART nanoparticles have uniform particle size,good dispersibility,smooth surface without blocking,and good stability.1.Through the established content analysis method,the drug content of artesunate in HA-ART was 20%.In vitro release studies have shown that HA-ART polymer nanoparticles have better release characteristics and no obvious burst release behavior.2.Experiment with the prepared HA-ART nanoparticles to study the effects of HA-ART nanoparticles on the vitality and proliferation of two breast cancer cells MCF-7,MDA-MB-231 and human normal breast cells MCF10 A.The results show that HA-ART nanoparticles can significantly inhibit the viability and proliferation of breast cancer cells in vitro,but have no significant effect on the growth of MCF10 A cells.3.The effects of HA-ART on the migration and invasion ability of breast cancer cells MCF-7 and MDA-MB-231 were detected by scratch healing,cell migration,and cell invasion experiments.The results showed that compared with the control group,the migration and invasion ability of cells in the HA-ART group was significantly reduced.The cell cycle distribution experiment results show that HA-ART can block MCF-7 and MDA-MB-231 cells in the G2/M phase,and the cycle-related protein results are consistent with the flow cytometry results.Flow cytometry,Western blot and Tunel apoptosis experiments were used to investigate the effect of HA-ART on apoptosis and autophagy of MCF-7 and MDA-MB-231 cells.The results showed that HA-ART can induce apoptosis and autophagy.Phagocytosis,and the HA-ART effect was significantly enhanced compared with the ART group.In summary,we have successfully prepared HA-ART nanoparticles,which can be used as a superior drug delivery system to enhance the anti-tumor activity of ART and achieve targeted therapy for breast cancer.