Increase of the pharmacological and pharmacokinetic efficacy of negatively charged polypeptide recombinant hirudin in rats via parenteral route by association with cationic liposomes
Research article published in Journal of controlled release : official journal of the Controlled Release Society (2008)
Abstract
Two biodegradable cationic lipids, stearylamine and DC-Chol, were chosen to investigate the effect of cationic lipids on the in vitro and in vivo characteristics of hydrophilic proteins or peptides of low isoelectric point. Thrombin inhibitor recombinant hirudin variant-2 (rHV2) was selected as the model drug. The cationic lipids were found to achieve higher entrapment efficiency of rHV2 in liposomes than zwitterionic lipids. The positively charged liposomes became less positive and relatively stable in serum after loading rHV2. The cationic liposomes induced sustained release of rHV2 in the presence of plasma, significantly prolonged the antithrombotic efficacy and plasma level of rHV2 after intravenous injection in rats in comparison with neutral lipid liposomes, especially for stearylamine group. Both clotting times correlated well with plasma rHV2 levels. No serious adverse events were observed and physical state of rats was satisfactory for all the formulations. Electrostatic interaction between negative charge of rHV2 and cationic liposomes was confirmed and it might affect all the characteristics of rHV2 loaded cationic vehicles. The findings suggest that cationic liposomes may be a potential sustained-release delivery system for parenteral administration of hydrophilic proteins or peptides with low isoelectric point to prolong efficacy and improve bioavailability.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Two biodegradable cationic lipids, stearylamine and DC-Chol, were chosen to investigate the effect of cationic lipids on the in vitro and in vivo characteristics of hydrophilic proteins or peptides of low isoelectric point.
Por qué esto importa para la hirudoterapia
Este estudio investigó si los liposomas catiónicos (estearilamina y DC-Chol) podían mejorar la administración de la variante 2 de hirudina recombinante (rHV2), descrita en el resumen como un inhibidor de la trombina con carga negativa y fármaco modelo, en ratas. Los liposomas catiónicos lograron un mayor atrapamiento, indujeron una liberación sostenida de rHV2 en plasma y prolongaron significativamente la eficacia antitrombótica y los niveles plasmáticos de rHV2 tras la inyección intravenosa en comparación con los liposomas neutros, mostrando el grupo de estearilamina el efecto más intenso. Esto puede ser relevante para el ámbito de la ASH porque la hirudina es ampliamente reconocida como un anticoagulante derivado de sanguijuela, aunque el resumen en sí no establece este origen. Se trata de un estudio preclínico en animales sin participación de sanguijuelas, centrado en la tecnología de administración de fármacos en lugar de en la hirudoterapia.
Citación
Increase of the pharmacological and pharmacokinetic efficacy of negatively charged polypeptide recombinant hirudin in rats via parenteral route by association with cationic liposomes
Meng M et al. · Journal of controlled release : official journal of the Controlled Release Society, 2008
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026