The Preparation Of Star-like Polymerwithmatrixmetal-loprot Einase Eleavable Peptide Nanoparticles And Its Pharmacokinetics

Cancer is an urgent problem to be solved in the field of international medical field.The traditional chemotherapy drugs to cancer cells has low selectivity,at the same time,will cause damage to normal cells,which can cause a variety of side effects.In addition,the traditional chemotherapeutic drugs are usually difficult to reach the treatment concentration in the body because of poor water solubility,which limits their pharmacological effects.With the further research of cancer treatment,Nano drug carriers in the fields of biology,materials,medicine and other fields of application prospect is more broad.The main way to solve these problems is to pack the drug in a suitable carrier,which can improve drug solubility and bioavailability andachieve tumor targeted drug delivery,reduce the side effects of drugs,improve the drug efficacy.In the new material field,degradable materials with star-like structure have been paid much attention,owing to their advantages,such as more functional polymer chains and strong controllability properties.It can connect two or more materials with different properties through a central node,so as to form a polymer material with composite properties.Curcumin is a kind of phenolic compound,which is extracted from Curcuma longa.Research shows that curcumin has antioxidant,antiinfectionand antitumor characteristics.Curcumin is a kind of effective MDR?multidrug resistance?inhibitor,and has been shown to be effective,in Pharmacopoeia dose,no adverse reaction.Curcumin has a very good application prospect in the tumor of treatment.However,the structure of it is not stable,the water solubility is poor.And it is difficult to be absorbed.In order to raise the bioavailability of the curcuminand have the best therapeutic purpose,dosage modification has become a focal point.According to the present situation and probiem,curcumin was selected as a drug model.Amphiphic star-like polymerwith matrix metalloproteinase-eleavable peptide?XGPLGIAGQr9X.?was studied.TCL-Peptide-PEG was synthesized.The residence time and stability of the drug in vivo were increased by the hydrophilic block modification and the drug loading was increased by the modification of the star-like polymer.The main research contents and results were shown as follows:?1?TCL-Peptide-PEG with amphiphic star-like properties wassynthesized.And it was charactered byFT-IR and ¹H-NMR analysis.A GPC method was established to analysis the molecular weight of polymers.The peptide bond was tested by BCA method.The results of FT-IR and ¹H-NMR analysis shows that TCL-Peptide-PEG was successful synthesized.The result also shows that the content of peptide in Peptide-PEG was about 69.27%.The content of Peptide in Tri-CL-Peptide-PEG was about 26.91%.?2?Curcuminnanoparticles were made by microchannel method.With Curcumin loading and particle size as basic factors,the influence of aqueous phaseflow rate,lipid phase flow rate,the concentration of aqueous phase,the concentration of lipid phase and the concentration of curcumin phase were investigated by single factor experiment of microchannels.The preparation process was optimized by BBD response surface method.The optimal condition was:the water phase flow rate was 0.43 ml/min,the oil phase flow rate was 0.53 ml/min,the aqueous phase concentration was 2.17 mg/ml,the oil phase concentration was6.67 mg/ml,and the drug concentration was 0.18 mg/ml.The entrapment efficiency was?91.63+0.88?%,the particle size was?112.5+2.06?nm,Zeta was-9.77mv.The surface of curcumin nanoparticles was observed by TEM,which were spherical.IR results showed that curcumin was wrapped in the material ofTCL-Peptide-PEG.?3?A preliminary study on the pharmacodynamics of Cur-NPs showed:Hela cells growth was inhibitedby Cur-NPs whose concentration was 6.25?mol·L^-1?12.5?mol·L^-1?25?mol·L^-1?50?mol·L-1?100?mol·L^-1.The inhibition rate was 19.77%⁶0.15%,which was in a concentration and time dependent?0-72h?,Cur-NPs and Cur-DMSO were compared.Cur-NPs were observed by fluorescence microscopy,which has an obvious nature of entry into the cell.?4?A preliminary study on pharmacokinetics of Cur-NPs:The in vitro drug release properties of the nanoparticles were investigated,and the distribution of the drug in rats was studied.The rats with drug experimentin vivo showed that showed that the Cur-DMF was metabolized in 240 min.In contrast,the retention time of Cur-NPs was showed 480min.The Cur-NPs was been provedto prolong the retention time of the drug in the rat body.In conclusion,amphiphic star-like polymer with matrix metalloproteinase-eleavable peptide is potential application in the drug delivery.