The stabilization and release of hirudin from liposomes or lipid-assemblies coated with hydrophobically modified dextran
Research article published in AAPS PharmSciTech (2000)
Abstract
Hirudin is a 65-amino acid peptide and the most potent and specific known inhibitor of thrombin (K(i) = 0.2 pM). The short elimination half-life of hirudin from the body (1 hour) necessitates the use of a sustained and controlled delivery system. A proliposome method was used to entrap hirudin in liposomes coated with palmitoyl dextran-coated liposomes and lipid-assemblies. In vitro release studies of hirudin were performed using the lipid systems enclosed in dialysis membranes or deposited in the pores of a vascular graft. The activity of hirudin and released hirudin was measured using a thrombin chromogenic substrate assay. Entrapment efficiencies of hirudin in lipid-assemblies approached 100%, however, the release of hirudin from these systems was rapid with 90% released in 17 hours. Entrapment efficiencies of hirudin in coated-liposomes ranged from 5% to 55% and were dependent on several variables. Palmitoyl dextran- coated-liposomes showed a burst of 30% hirudin released in 5 hours with an additional 10% to 35% released over the next 600 hours. In all samples, 30-40% of the hirudin remained associated with the lipid-systems even after 600 hours. The released hirudin retained only 33% of its ability to inhibit thrombin when released from uncoated liposomes. However, hirudin retained 95% of its thrombin inhibitory activity when released from palmitoyl dextran-coated liposomes. Coated liposomes were found to stabilize hirudin and result in greater retention of hirudin's ability to inhibit thrombin's enzymatic activity, although the mechanism is not yet understood.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Hirudin is a 65-amino acid peptide and the most potent and specific known inhibitor of thrombin (K(i) = 0.2 pM).
Por qué esto importa para la hirudoterapia
El resumen evaluó sistemas de administración liposomales y de ensamblaje lipídico recubiertos con dextrano palmitoilo para la liberación sostenida de hirudina, descrita como un péptido de 65 aminoácidos y el inhibidor conocido más potente y específico de la trombina (Ki = 0.2 pM), con una semivida de eliminación de aproximadamente una hora. Los liposomas recubiertos con dextrano palmitoilo retuvieron el 95% de la actividad inhibidora de la trombina de la hirudina tras su liberación, frente al 33% de los liposomas sin recubrimiento, con una liberación sostenida durante 600 horas. Esto aborda la administración y la estabilidad de la hirudina, un inhibidor de la trombina, lo cual es relevante para el ámbito de ASH. Salvedad: se trata de un estudio de formulación y de administración de fármacos in vitro, sin datos in vivo, en animales ni clínicos, y el resumen no menciona sanguijuelas ni terapia con sanguijuelas.
Citación
The stabilization and release of hirudin from liposomes or lipid-assemblies coated with hydrophobically modified dextran
Mumper RJ et al. · AAPS PharmSciTech, 2000
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026