A Study On The Preparation Process Of Drug-loaded Nanoparticles Vascular Scaffold Coating Based On Electrophoretic Deposition

Drug-eluting stent(DES)has become the first choice instrument for interventional treatment of cardiovascular diseases because of its minimally invasive,high efficiency and can significantly reduce the incidence of restenosis after the interventional therapy.The drug-loaded stent coating is the most important structure of DES distinguished from the traditional bare metal stent(BMS).It is an important medium connecting the stent platform with the vascular wall of the lesion site,and often associated with severe postoperative complications such as post-stent thrombosis,delayed endothelialization,and chronic inflammation,which makes the stent coating technology an extremely important part in DES research.At present,the preparation of DES drug-loaded coatings mainly using physical methods,such as dip-coating and spray-coating.Based on nano drug-loading technology and modern electrochemical technology,electrophoretic deposition(EPD)and self-assembly(SAM)of drug-loaded nanoparticles can realize the combination of drug-loaded nanoparticles with the stent,and overcome the defects of traditional physical methods to a certain extent.In this paper,a RAPA-PLGA-NPs-loaded drug-eluting stent coating was prepared based on the EPD principle,and the results are as follows:(1)The rapamycin-loaded PLGA nanoparticles were prepared by emulsion solvent evaporation method.The content of rapamycin was detected by high performance liquid chromatography(HPLC)method,and established the chromatographic conditions,standard curves and methodological investigation.The effects of surface emulsifier polyacrylic acid(PAA)concentration,water-oil phase volume ratio,concentration of drug carrier PLGA and concentration of drug RAPA on drug loading amount and encapsulation efficiency of RAPA-PLGA-NPs in the preparation process were studied by single factor experiments.Through orthogonal experiment optimization,the optimal preparation process of drug-loaded nanoparticles was found to be: PAA concentration of 0.2%,water and oil ratio of 20:1,PLGA concentration of 25 mg/ml,and RAPA concentration of 3 mg/ml.Based on the optimized experimental parameters,the average drug loading amount of drug-loaded nanoparticles was 5.57±0.12%,and the average encapsulation efficiency was 51.94±1.13%,with a good stability and repeatability.(2)An experimental platform for the preparation of nanoparticles-loaded stent coatings was established based on EPD principle,and prepared the rapamycin-loaded nanoparticles stent coating.The effects of deposition voltage,deposition time and concentration of deposition solute on the drug loading amount of the stent and the thickness,surface quality of the stent coating were studied by single factor experiments.Through orthogonal experiment optimization,the optimal preparation process of stent coating was found to be: deposition voltage of 7V,deposition time of 25 min,deposition liquid solute concentration of 1.3mg/ml.Based on the optimized parameters,the average drug loading amount of the RA-PA-PLGA-NPs-loaded drug-eluting stent was 91.72±7.74 ug,with a stable and controllable drug loading amount,uniform surface morphology,and the binding force with the stent substrate is good.(3)The drug release characteristics of the RAPA-PLGA-NPs-loaded drug-eluting stent prepared by EPD method were studied based on the constant temperature oscillation method.According to the experimental results,the in vitro drug release profile of the stent was established.The results showed that the release rate of the drug-loaded nanoparticle stent was first fast and then slower.The release rate of 1h was about 24.44%,and 24 h was about 42.23%(the phenomenon of sudden release of drug was not observed within one day),then the rate of drug release gradually slowed down.The cumulative release of drug in 16 days exceeded 90%.And the release of the drug is basically completed in 28 days.By comparing and analyzing the release curves of several commercial rapamycin-eluting stents,it is shown that the RAPA-PLGA-NPs-loaded drug-eluting stent prepared by EPD method has a good drug sustained release characteristics.