Nano-anticoagulant based on carrier-free low molecular weight heparin and octadecylamine with an albumin shuttling effect.
Nat Commun
; 15(1): 6769, 2024 Aug 08.
Article
em En
| MEDLINE
| ID: mdl-39117649
ABSTRACT
Low-molecular-weight heparin (LMWH), derived from unfractionated heparin (UFH), has enhanced anticoagulant efficacy, long duration of action, and extended half-life. Patients receiving LMWH for preventive therapies would strongly benefit from its long-term effects, however, achieving this is challenging. Here, we design and evaluate a nanoengineered LMWH and octadecylamine conjugate (LMHO) that can act for a long time while maintaining close to 97 ± 3% of LMWH activity via end-specific conjugation of the reducing end of LMWH. LMHO can self-assemble into nanoparticles with an average size of 105 ± 1.7 nm in water without any nanocarrier and can be combined with serum albumin, resulting in a lipid-based albumin shuttling effect. Such molecules can circulate in the bloodstream for 4-5 days. We corroborate the self-assembly capability of LMHO and its interaction with albumin through molecular dynamics (MD) simulations and transmission electron microscopy (TEM) analysis. This innovative approach to carrier-free polysaccharide delivery, enhanced by nanoengineered albumin shuttling, represents a promising platform to address limitations in conventional therapies.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Heparina de Baixo Peso Molecular
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Nanopartículas
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Simulação de Dinâmica Molecular
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Aminas
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Anticoagulantes
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article