VEGF-PLGA Release Particles For Angiogenesis To Rabbit Myocardial Infarction

Part I Preparation and Feature Detection of VEGF-PLGA Release ParticlesObjective:1 To prepare lactic-acid/glycolic-acid (PLGA) carrying Vascular Endo-thelial Growth Factor (VEGF) sustained-release polymer particles.2 Detected the basic physical properties, release characteristics in vitro, also ultrasound imaging effect both in vivo and in vitro of the polymer particles.Methods:1 The sustained-release polymer particles ultrasound contrast agents carrying VEGF were prepared with PLGA that could be biodegradable by double emulsion evaporation method and freeze drying techniques.2 Morphological observation and analysis of particle size and drug distribution were detected used inverted optical microscope and scanning electron microscopy, Release characteristics of the polymer particles in vitro was detected by Elisa enzyme-linked immunosorbent assay, observed ultrasound imaging effect in vivo.Results:1 Preparation of the VEGF-PLGA contrast agent Successful and got a high encapsulation efficiency also drug loading efficiency.2 The VEGF-PLGA sustained-release particles with the rules of spherical, uniform size and good dispersion under the light microscope, while had the round shape, smooth surface under the electron microscope. The average size of VEGF-PLGA particles was 2.0μm, average encapsulation efficiency was 82.7% and average drug loading efficiency was 5.97%. In vitro experiment showed that in the initial 6h, VEGF released by sustained-release particles was about 10%, VEGF was about 75% 30 days later. VEGF-PLGA particles also with a good imaging effect in vivo.Conclusions:Sustained-release effect of the polymer particles ultrasound contrast agents prepared with double emulsion evaporation method and freeze drying techniques was obvious. The particles also with better ultrasound imaging in vivo, low toxicity and conform with the basic requirements of an ideal drug carrier.PARTⅡTreatment of acute myocardial infarction in rabbits used VEGF-PLGA particles sustained-releaseObjective:Observed the effect of promoting angiogenesis and treatment of myocardial remodeling after treatment of acute myocardial infarction in New Zealand white rabbits used VEGF-PLGA particles sustained-release.Methods:30 New Zealand white rabbits were randomly divided into 4 groups after the models of myocardial infarction were prepared.①VEGF-PLGA group,②VEGF group,③PLGA group,④control group. Drugs were injection from myocardial five days after Models were prepared. Cardiac mobility was evaluated by echocardiography and ECG after treatment for 4 weeks. All the rabbits were sacrificed and the CD34 expression was detected by IHC, and Microvessel density (MVD) was determined under the microscope. The Ang-1 expression was detected by IHC. The expression of VEGF protein was respectively detected by ELISA and Western blot.Results:IHC showed that CD34 of VEGF-PLGA group was the highest among all the groups with the MVD (43.50±2.89/HP). The expression of VEGF protein detected by ELISA and Western blot of VEGF-PLGA group was higher than those of other groups (P<0.05).Conclusions:VEGF-PLGA sustained-release particles can promote angiogenesis and improve cardiac function after acute myocardial infarction. PartⅠPreparation and Feature Detection of VEGF-PLGA Release ParticlesObjective:1 To prepare lactic-acid/glycolic-acid (PLGA) carrying Vascular Endo-thelial Growth Factor (VEGF) sustained-release polymer particles.2 Detected the basic physical properties, release characteristics in vitro, also ultrasound imaging effect both in vivo and in vitro of the polymer particles.Methods:1 The sustained-release polymer particles carrying VEGF were prepared with PLGA which could be biodegradable by double emulsion evaporation method and freeze drying techniques.2 Morphological observation, size of particle and drug distribution were detected using inverted optical microscope and scanning electron microscopy, Release characteristics of the polymer particles in vitro was detected by Elisa enzyme-linked immunosorbent assay, the imaging effect was observed in vivo.Results:1 Preparation of the VEGF-PLGA sustained-release particles was successful and got a high encapsulation efficiency also drug loading efficiency.2 The VEGF-PLGA sustained-release particles with the rules of spherical, uniform size and good dispersion under the light microscope, while had the round shape, smooth surface under the electron microscope. The average size of VEGF-PLGA particles was 2.0μm, average encapsulation efficiency was 82.7% and average drug loading efficiency was 5.97%. In vitro experiment showed that in the initial 6h, VEGF released by sustained-release particles was about 10%, VEGF was about 75% 30 days later. VEGF-PLGA particles also with a good imaging effect in vivo.Conclusions:Sustained-release effect of the polymer particles ultrasound contrast agents prepared with double emulsion evaporation method and freeze drying techniques was obvious. The particles also with better ultrasound imaging in vivo, low toxicity and conform with the basic requirements of an ideal drug carrier.PARTⅡTreatment of acute myocardial infarction in rabbits used VEGF-PLGA particles sustained-releaseObjective:Observed the effect of promoting angiogenesis and treatment of myocardial remodeling after treatment of acute myocardial infarction in New Zealand white rabbits used VEGF-PLGA sustained-release particles.Methods:30 New Zealand white rabbits were randomly divided into 4 groups after the models of acute myocardial infarction were prepared.①VEGF-PLGA group,②VEGF group,③PLGA group (EPCs),④Surgery alone group. Drugs were injection from myocardial four days after Models were prepared. Cardiac mobility was evaluated by echocardiography after treatment for 2 weeks. All the rabbits were sacrificed, The CD34 expression was detected by IHC, and Microvessel density (MVD) was determined under the microscope. The expression of VEGF protein was respectively detected by ELISA and Western blot methods.Results: IHC showed that CD34 of VEGF-PLGA group was the highest among all the groups with the MVD(43.50±2.89/HP). The expression of VEGF protein detected by ELISA and Western blot of VEGF-PLGA group was higher than those of other groups.Conclusions:VEGF-PLGA sustained-release particles can promote angioge-nesis and improve cardiac function after acute myocardial infarction.