RESUMO
BACKGROUND: To comparatively evaluate the cardioprotective activity of placental growth factor (PGF) delivered through direct injection and a nanoparticle-based system respectively and to study the underlying mechanisms in a rat model of acute myocardial infarction (AMI). METHODS: Poly lactic-co-glycolic acid (PLGA)-based PGF-carrying nanoparticles (PGF-PLGANPs) were created. The mean size and morphology of particles were analyzed with particle size analyzer and transmission electronic microscopy (TEM). Encapsulation efficiency and sustained-release dose curve were analyzed by ELISA. Sprague-Dawley rats were randomized into four groups (n = 10). While animals in the first group were left untreated as controls, those in the other 3 groups underwent surgical induction of AMI, followed by treatment with physiological saline, PGF, and PGF-PLGANPs, respectively. Cardiac function was evaluated by transthoracic echocardiography at 4 weeks after treatment. At 6 weeks, rats were sacrificed, infarction size was analyzed with Masson trichrome staining, and protein contents of TIMP-2, MT1-MMP and MMP-2 at the infarction border were determined by immunohistochemistry and western blotting analysis. RESULTS: PGF was released for at least 15 days, showing successful preparation of PGF-PLGANPs. Coronary artery ligation successfully induced AMI. Compared to physiological saline control, PGF, injected to the myocardium either as a nude molecule or in a form of nanoparticles, significantly reduced infarction size, improved cardiac function, and elevated myocardial expression of TIMP-2, MT1-MMP, and MMP-2 (P < 0.05). The effect of PGF-PLGANPs was more pronounced than that of non-encapsulated PGF (P < 0.05). CONCLUSION: Target PGF delivery to myocardium may improve cardiac function after AMI in rats. PLGA-based nanoparticles appear to be a better approach to delivery PGF. PGF exerts its cardioprotective effect at least partially through regulating metalloproteinase-mediated myocardial tissue remodeling.
Assuntos
Cardiotônicos/administração & dosagem , Portadores de Fármacos , Ácido Láctico/química , Infarto do Miocárdio/tratamento farmacológico , Nanopartículas , Ácido Poliglicólico/química , Proteínas da Gravidez/administração & dosagem , Animais , Cardiotônicos/química , Química Farmacêutica , Preparações de Ação Retardada , Modelos Animais de Doenças , Humanos , Injeções Intralesionais , Metaloproteinase 14 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Fator de Crescimento Placentário , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Proteínas da Gravidez/química , Ratos Sprague-Dawley , Proteínas Recombinantes/administração & dosagem , Solubilidade , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacosRESUMO
OBJECTIVE: To investigate lyophilization of SM-SLN. METHOD: The parameters of lyophilization process was optimized. In addition, the protective effect of various types and concentrations of cryoprotectants were tested by shape, colour and disparity. RESULT: The mixture of 2% lactose and 2% glucose could better prevent nanoparticles from aggregating, the optimal lyophilization process was followed: precooled at -45 degrees C for 10 hr; primary drying at -25 degrees C for 5 hr; secondary drying at 10 degrees C for 3 hr; finally drying at 30 degrees C for 6 hr. CONCLUSION: Changes in particle size distribution during lyophilization could be minimized by optimizing the parameters of the lyophilization process and adding supporting agent.
