| Anti-tumor drugs in clinical chemotherapy can cause pain to patients due to their need for long-term multiple injections.Sustained release systems refer to drug delivery formulations that are slowly released at a certain rate in the body after being encapsulated in specific materials,which can improve the therapeutic effect of diseases.Poly(lactic acid)has extremely high stability,can be digested and absorbed by body tissues,and can be decomposed into carbon dioxide and water in organisms.It has good biocompatibility and biodegradability,and is therefore recognized as a safe excipient with great potential for development in pharmaceutical sustained-release systems.This project uses polylactic acid,which has a wide range of sources,low manufacturing cost,good biocompatibility,biodegradability,and is non-toxic and harmless,as a drug carrier sustained-release material.5-fluorouracil(5-Fu)is used as a model drug,purified by ion exchange method,and other impurities are removed.Then,5-Fu polylactic acid microspheres are prepared by emulsification solvent evaporation method.Finally,their properties are comprehensively characterized and studied,in order to provide experiments and guidance for their practical application.The content and results of this research project are as follows:1)Purification of 5-Fu.Further removal of impurities in 5-Fu through ion exchange method.The experimental results showed that with p H=8,initial concentration of 11.0 g/L,filling amount of 60 g,and flow rate of 0.5 m L/min,adsorption was carried out,and the final adsorption amount was 0.0785 g/g.Then wash the impurities with pure water at an appropriate flow rate of 1 m L/min;Finally,a dilute hydrochloric acid solution of 0.03 mol/L was eluted at an appropriate flow rate of 1 m L/min to obtain a high-purity 5-Fu eluent.The sample was obtained by rotary evaporation,with a purity of 99.99%.2)The emulsion solution evaporation method was used to extract polylactic acid microspheres,and the profound effects of surfactant type,content,and polylactic acid content on the shape of microspheres were deeply studied.The experimental results showed that when Tween 20 was used as surfactant,the concentration was controlled at 0.03 g/m L,the content of PLA was 0.02 g/m L,and the weight ratio of organic phase to aqueous phase was 1:10,the morphology of PLA microspheres changed significantly,showing good structural stability and corrosion resistance.After careful preparation,the polylactic acid microspheres have a perfect shape,uniform size,and particle size ranging from 50 to 70μm.3)After comparison,it was found that the content ratio of 5-Fu to polylactic acid was 1:6,and the optimal preparation process was used to stabilize the concentration of polylactic acid at 0.02 g/m L,the mass ratio of organic phase to aqueous phase was1:10,and the level of Tween 20 was also stable at 0.03 g/m L.Therefore,it can be concluded that the preparation process of 5-Fu polylactic acid microspheres under this condition is the best.The prepared polylactic acid microspheres have a round morphology and uniform particle size,approximately(65±12.5)μm.4)In vitro release studies.After constant temperature oscillation method measurement,it was found that the drug 5-fluorouracil released from phosphate buffer at different time periods has a good sustained-release effect.In the early stage of sustained release,the drug will be released quickly,and then slowly.By using the first-order kinetic equation,the in vitro release behavior of 5-Fu polylactic acid loaded microspheres can be better simulated,with y=87.88703(1-exp(-0.01765x))and R~2=0.993.This indicates that the interpretation of the drug mainly consists of two parts:the sudden release phase and the sustained release phase.5)Molecules automatically dock with 5-Fu and polylactic acid molecules. |
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