Supramolecular Prodrug Hydrogel for One-Week Protection Against Thrombosis
Basic science / preclinical published in Small (2025)
Abstract
In clinical anticoagulant therapy, the drug Bivalirudin (Biva) presents a lower incidence of adverse events and more predictable pharmacokinetics in comparison to heparin. However, its short half-life of ≈20 min leads to poor patient compliance and increased medical burden. Here, a long-acting anticoagulant hydrogel based on Biva for antithrombotic treatment is described. The fusion peptide (d-RADA)8-B that integrates Biva, a D-type self-assembly motif, and an activated factor X (FXa)-responsive motif exhibits both supramolecular reservoir and prodrug-like properties. After subcutaneous injection, the anticoagulant peptide forms a semi-solid depot with protease-degradation resistance and slowly disassembles to release prodrug (d-RADA)8-B into the bloodstream. The circulating prodrug acts as an inert sentinel, which can be activated to release Biva to inhibit thrombus formation when exposed to the thrombus-related protease FXa. One week after the administration of (d-RADA)8-B, significant embolism suppression is observed in animal models of carotid artery thrombosis and pulmonary embolism without increasing hemorrhagic side effects. This study demonstrates a concise strategy to engineer a supramolecular anticoagulant hydrogel with long-term, high drug loading, and on-demand antithrombotic activation.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Engineered supramolecular prodrug hydrogel using bivalirudin (the leech-hirudin-derived direct thrombin inhibitor) with a FXa-responsive linker, achieving one-week sustained thrombosis prevention in animal models without increased bleeding risk.
Por qué esto importa para la hirudoterapia
Este estudio describe una formulación de hidrogel supramolecular de bivalirudina, un inhibidor directo de la trombina derivado de la hirudina — el anticoagulante distintivo del secretoma de la sanguijuela medicinal. El hidrogel emplea un diseño de profármaco sensible al FXa que permite una liberación sostenida, y en modelos animales de trombosis de la arteria carótida y embolia pulmonar produjo una semana de supresión significativa de embolias sin aumentar los efectos adversos hemorrágicos. Este trabajo es relevante para ASH porque aborda la vida media muy corta (~20 min) que ha limitado el uso clínico de los anticoagulantes basados en hirudina, extendiendo potencialmente la utilidad terapéutica de los fármacos inspirados en el secretoma de la sanguijuela. Una advertencia honesta: estos son resultados preclínicos únicamente en modelos animales; la formulación no ha sido probada en humanos, y el estudio concierne a un profármaco de bivalirudina más que a la terapia con sanguijuelas en sí misma.
Citación
Supramolecular Prodrug Hydrogel for One-Week Protection Against Thrombosis.
Zhang W et al. · Small, 2025
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026