Development and in vitro characterization of polymeric nanoparticles containing recombinant adrenomedullin-2 intended for therapeutic angiogenesis.
Int J Pharm
; 576: 118997, 2020 Feb 25.
Article
em En
| MEDLINE
| ID: mdl-31893542
ABSTRACT
Cardiovascular 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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Portadores de Fármacos
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Hormônios Peptídicos
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Células Endoteliais
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Indutores da Angiogênese
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Proliferação de Células
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Copolímero de Ácido Poliláctico e Ácido Poliglicólico
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Int J Pharm
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Brasil