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Pharm Res ; 33(5): 1191-203, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26812966

RESUMO

PURPOSE: Nanoparticle (NP) attachment to biocompatible secondary carriers such as red blood cell (RBC) can prolong blood residence time of drug molecules and help create next-generation nanotherapeutics. However, little is known about the impact of RBC-targeted NPs on erythrocyte function. METHODS: The objectives of this study were to develop and characterize in vitro a novel poly-L-lysine (PLL) and polyethylene glycol (PEG) copolymer-based NP containing fluorescent-tagged bovine serum albumin (BSA), and conjugated with ERY1, a 12 amino acid peptide with high affinity for the RBC membrane protein glycophorin A (ENP). RESULTS: Confocal and flow cytometry data suggest that ENPs efficiently and irreversibly bind to RBC, with approximately 70% of erythrocytes bound after 24 h in a physiologic flow loop model compared to 10% binding of NPs without ERY1. Under these conditions, synthesized ENPs were not toxic to the RBCs. The rheological parameters at the applied shear. (0-15 Pa) were not influenced by ENP attachment to the RBCs. However, at high concentration, the strong affinity of ENPs to the glycophorin-A reduced the deformability of the RBC. CONCLUSIONS: ENPs can be efficiently attached to the RBCs without adversely affecting cellular function, and this may potentially enhance circulatory half-life of drug molecules.


Assuntos
Sistemas de Liberação de Medicamentos , Membrana Eritrocítica/metabolismo , Glicoforinas/metabolismo , Nanopartículas/metabolismo , Peptídeos/metabolismo , Animais , Bovinos , Deformação Eritrocítica , Eritrócitos/citologia , Eritrócitos/metabolismo , Camundongos , Nanopartículas/química , Peptídeos/química , Polietilenoglicóis/química , Polietilenoglicóis/metabolismo , Polilisina/química , Polilisina/metabolismo , Soroalbumina Bovina/administração & dosagem
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