Protein-functionalized nanoparticles derived from end-functional polymers and polymer prodrugs for crossing the blood-brain barrier.
Eur J Pharm Biopharm
; 142: 70-82, 2019 Sep.
Article
em En
| MEDLINE
| ID: mdl-31176723
ABSTRACT
Nanoparticles may provide a viable way for neuroprotective drugs to cross the blood-brain barrier (BBB), which limits the passage of most drugs from the peripheral circulation to the brain. Heterotelechelic polymer prodrugs comprising a neuroprotective model drug (adenosine) and a maleimide functionality were synthesized by the "drug-initiated" approach and subsequent nitroxide exchange reaction. Nanoparticles were obtained by nanoprecipitation and exhibited high colloidal stability with diameters in the 162-185â¯nm range and narrow size distributions. Nanoparticles were then covalently surface-conjugated to different proteins (albumin, α2-macroglobulin and fetuin A) to test their capability of enhancing BBB translocation. Their performances in terms of endothelial permeability and cellular uptake in an in vitro BBB model were compared to that of similar nanoparticles with surface-adsorbed proteins, functionalized or not with the drug. It was shown that bare NPs (i.e., NPs not surface-functionalized with proteins) without the drug exhibited significant permeability and cellular uptake, which were further enhanced by NP surface functionalization with α2-macroglobulin. However, the presence of the drug at the polymer chain-end prevented efficient passage of all types of NPs through the BBB model, likely due to adecrease in the hydrophobicity of the nanoparticle surface and alteration of the protein binding/coupling, respectively. These results established a new and facile synthetic approach for the surface-functionalization of polymer nanoparticles for brain delivery purposes.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polímeros
/
Pró-Fármacos
/
Barreira Hematoencefálica
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Proteínas
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Nanopartículas
Limite:
Humans
Idioma:
En
Revista:
Eur J Pharm Biopharm
Ano de publicação:
2019
Tipo de documento:
Article