2 research outputs found
Clot-Targeted Micellar Formulation Improves Anticoagulation Efficacy of Bivalirudin
Application of anticoagulants remains the primary strategy for prevention and treatment of thrombosis. However, high rate of bleeding complications limits their use. The peptide anticoagulant bivalirudin has been reported to exhibit a lower rate of bleeding complications than heparin, and it also has the advantage of not causing thrombocytopenia, which is a problem with heparin. Nonetheless, hemorrhage is the most common complication of bivalirudin therapy, and there is no effective antidote. Here we use a thrombus-binding peptide, CR(<i>N</i>Me)EKA, to accomplish selective delivery of the bivalirudin-carrying micellar nanocarrier to sites of thrombosis. Bivalirudin and CR(<i>N</i>Me)EKA, each with a PEG-lipid tail, spontaneously assembled into 30 nm micelles, which almost completely retained the anticoagulant activity of bivalirudin. The micellar formulations exhibited high stability both <i>in vitro</i> and <i>in vivo</i>. In a thromboplastin-induced mouse thrombosis model, the targeted micelles accumulated in lung thrombi 10-fold more than nontargeted micelles. Moreover, the micellar formulation significantly prolonged the half-life and thereby increased the bioavailability of bivalirudin. The micellar bivalirudin had significantly higher anticoagulant activity than free bivalirudin in both the lung thrombosis model and a ferric chloride-induced carotid artery thrombosis model. The specific targeting of thrombi demonstrated here makes it possible to increase the efficacy of bivalirudin as an anticoagulant. Alternatively, the dose could be reduced without loss of efficacy to lower the systemic exposure and improve safety
Small GSH-Capped CuInS<sub>2</sub> Quantum Dots: MPA-Assisted Aqueous Phase Transfer and Bioimaging Applications
An efficient ligand exchange strategy
for aqueous phase transfer
of hydrophobic CuInS<sub>2</sub>/ZnS quantum dots was developed by
employing glutathione (GSH) and mercaptopropionic acid (MPA) as the
ligands. The whole process takes less than 20 min and can be scaled
up to gram amount. The material characterizations show that the final
aqueous soluble samples are solely capped with GSH on the surface.
Importantly, these GSH-capped CuInS<sub>2</sub>/ZnS quantum dots have
small size (hydrodynamic diameter <10 nm), moderate fluorescent
properties (up to 34%) as well as high stability in aqueous solutions
(stable for more than three months in 4 °C without any significant
fluorescence quenching). Moreover, this ligand exchange strategy is
also versatile for the aqueous phase transfer of other hydrophobic
quantum dots, for instance, CuInSe<sub>2</sub> and CdSe/ZnS quantum
dots. We further demonstrated that GSH-capped quantum dots could be
suitable fluorescence markers to penetrate cell membrane and image
the cells. In addition, the GSH-capped CuInS<sub>2</sub> quantum dots
also have potential use in other fields such as photocatalysis and
quantum dots sensitized solar cells