Quadros, Helenita CostaSantos, Laís de Macêdo FerreiraMeira, Cássio SantanaKhouri, Mariana IvoMattei, BrunoSoares, Milena Botelho PereiraBorges, William de CastroFarias, Leonardo PaivaFormiga, Fabio Rocha2020-04-242020-04-242019QUADROS, H. C. et al. Development and in vitro characterization of polymeric nanoparticles containing recombinant adrenomedullin-2 intended for therapeutic angiogenesis. International Journal of pharmaceutics, v. 576, p. 118997, fev. 2019. Disponível em: <https://www.sciencedirect.com/science/article/pii/S0378517319310580?via%3Dihub>. Acesso em: 10 fev. 2020.0378-5173http://www.repositorio.ufop.br/handle/123456789/12099Cardiovascular diseases (CVD) are the leading cause of death worldwide. Growth factor therapy has emerged as novel therapeutic strategy under investigation for CVD. In this sense, adrenomedullin-2 (ADM-2) has been recently identified as a new angiogenic factor able to regulate the regional blood flow and cardiovascular function. However, the therapeutic value of ADM-2 is limited by its short biological half-life and low plasma stability. Poly (lactic-co-glycolic acid) (PLGA) micro- and nanoparticles have been investigated as growth factor delivery systems for cardiac repair. In this study, we aimed to develop PLGA nanoparticles containing ADM-2 intended for therapeutic angiogenesis. PLGA nanoparticles containing ADM-2 were prepared by a double emulsion modified method, resulting in 300 nm-sized stable particles with zeta potential around – 30 mV. Electron microscopy analysis by SEM and TEM revealed spherical particles with a smooth surface. High encapsulation efficiency was reached (ca.70%), as quantified by ELISA. ADM-2 associated to polymer nanoparticles was also determined by EDS elemental composition analysis, SDS-PAGE and LC-MS/MS for peptide identification. In vitro release assays showed the sustained release of ADM-2 from polymer nanoparticles for 21 days. Cell viability experiments were performed in J774 macrophages and H9c2 cardiomyocyte cells, about which PLGA nanoparticles loaded with ADM-2 did not cause toxicity in the range 0.01–1 mg/ml. Of note, encapsulated ADM-2 significantly induced cell proliferation in EA.hy926 endothelial cells, indicating the ADM-2 bioactivity was preserved after the encapsulation process. Collectively, these results demonstrate the feasibility of using PLGA nanoparticles as delivery systems for the angiogenic peptide ADM-2, which could represent a novel approach for therapeutic angiogenesis in CVD using growth factor therapy.en-USrestritoPoly (lactic-co-glycolic acid)Protein deliveryArtigo publicado em periodicohttps://www.sciencedirect.com/science/article/pii/S0378517319310580?via%3Dihubhttps://doi.org/10.1016/j.ijpharm.2019.118997