| Thrombosis can form in any position in the blood vessels,which threatens human health and life all the time.Therefore,the major point of current researches is the thrombosis-targeted therapy and reducing its side effects.In this study,there are 3 parts of researches:（1）Construction a chronic animal inflammatory model by polylactic acid-glycolic acid copolymer.Firstly,the drug loaded microcapsules with a particle size of 712.53±28.96nm were obtained by optimizing the preparation process.It was found that the drug release of the carrier was in accordance with the first-order release equation.From the study on the animal inflammation model,it was found that the microencapsulated LPS was mainly concentrated in the liver,lungs and kidneys after the tail vein injection of mice,and the inflammatory reaction time was longer than that of pure LPS,indicating that PLGA embedded LPS could increase the inflammatory time and reduce the number of inflammatory drugs administered through its slow release effect;（2）Constructing and optimizing PLGA-PEG long circulating drug sustained release nanoparticles matrix.The improved five step double emulsion solvent evaporation method was utilized for the preparation scheme.With bovine serum albumin（BSA）as the model drug,the concentration of mixed surfactant in the oil phase,the concentration of PLGA-PEG,the volume of dispersed phase,the concentration of drug,the concentration of PVA,and the composition of organic solvent in the oil phase were investigated in a single factor manner.Based on these studies,three factors were selected then:the surface active concentration in the oil phase（X1）,the ratio of organic solvent in the oil phase（X2）,and the volume of dispersed phase（X3）,which were used to design the Box Behnken response surface experiment to determine the preparation process parameters as X1=10%,X2=0.5,X3=180ml.finally,the PEG-PLGA drug loaded microcapsules with a particle size of 159.84±1.52nm were obtained.The release behavior exhibited a typical three-stage release process,and its release model was consistent with the Weibull model.（3）Building targeted&sustained release system.According to the optimal preparation scheme obtained in the second part,CERKA-PEG-PLGA thrombus-targeted nanoparticles were synthesised by carbodiimide method.The size of the obtained particle was 196.53±10.99nm with the encapsulation efficiency of 69.53±1.15%,and the Zeta potential of-3.813±0.83m V.The infrared spectrum and X-ray photoelectron spectroscopy showed that CREKA peptide was successfully connected.Furthermore,it has no cytotoxicity in the range of 60-500ug/ml,and the nanoparticles have obvious thrombolytic performance on thrombus in vitro,and better thrombolytic performance than urokinase.It could be concluded that this system has great potential in targeted thrombolysis. |
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