Characterization of lysosome-destabilizing DOPE/PLGA nanoparticles designed for cytoplasmic drug release.
Int J Pharm
; 471(1-2): 349-57, 2014 Aug 25.
Article
em En
| MEDLINE
| ID: mdl-24882034
ABSTRACT
Polymeric nanoparticles (NPs) offer a promising approach for therapeutic intracellular delivery of proteins, conventionally hampered by short half-lives, instability and immunogenicity. Remarkably, NPs uptake occurs via endocytic internalization leading to NPs content's release within lysosomes. To overcome lysosomal degradation and achieve NPs and/or loaded proteins release into cytosol, we propose the formulation of hybrid NPs by adding 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) as pH sensitive component in the formulation of poly-lactide-co-glycolide (PLGA) NPs. Hybrid NPs, featured by different DOPE/PLGA ratios, were characterized in terms of structure, stability and lipid organization within the polymeric matrix. Experiments on NIH cells and rat primary neuronal cultures highlighted the safety profile of hybrid NPs. Moreover, after internalization, NPs are able to transiently destabilize the integrity of lysosomes in which they are taken up, speeding their escape and favoring cytoplasmatic localization. Thus, these DOPE/PLGA-NPs configure themselves as promising carriers for intracellular protein delivery.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfatidiletanolaminas
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Ácido Poliglicólico
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Soroalbumina Bovina
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Portadores de Fármacos
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Ácido Láctico
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Citoplasma
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Nanopartículas
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Lisossomos
Limite:
Animals
Idioma:
En
Revista:
Int J Pharm
Ano de publicação:
2014
Tipo de documento:
Article