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Nano-anticoagulant based on carrier-free low molecular weight heparin and octadecylamine with an albumin shuttling effect.
Lee, Jae-Hyeon; Lim, Hansol; Ma, Gaeun; Kweon, Seho; Park, Seong Jin; Seo, Minho; Lee, Jun-Hyuck; Yang, Seong-Bin; Jeong, Han-Gil; Park, Jooho.
Afiliación
  • Lee JH; Department of Biomedical Chemistry, College of Biomedical and Health Science, Konkuk University, Seoul, Republic of Korea.
  • Lim H; Department of Applied Life Science, BK21 Program, Konkuk University, Chungju, Republic of Korea.
  • Ma G; Department of Applied Life Science, BK21 Program, Konkuk University, Chungju, Republic of Korea.
  • Kweon S; Department of Applied Life Science, BK21 Program, Konkuk University, Chungju, Republic of Korea.
  • Park SJ; Department of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea. seho.kweon@chonnam.ac.kr.
  • Seo M; College of Pharmacy, Chonnam National University, Gwangju, Republic of Korea. seho.kweon@chonnam.ac.kr.
  • Lee JH; College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
  • Yang SB; Department of Biomedical Chemistry, College of Biomedical and Health Science, Konkuk University, Seoul, Republic of Korea.
  • Jeong HG; Department of Applied Life Science, BK21 Program, Konkuk University, Chungju, Republic of Korea.
  • Park J; Department of Applied Life Science, BK21 Program, Konkuk University, Chungju, Republic of Korea.
Nat Commun ; 15(1): 6769, 2024 Aug 08.
Article en 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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Heparina de Bajo-Peso-Molecular / Nanopartículas / Simulación de Dinámica Molecular / Aminas / Anticoagulantes Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Heparina de Bajo-Peso-Molecular / Nanopartículas / Simulación de Dinámica Molecular / Aminas / Anticoagulantes Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido