RESUMEN
Heparins are a family of sulfated linear negatively charged polysaccharides that have been widely used for their anticoagulant, antithrombotic, antitumor, anti-inflammatory, and antiviral properties. Additionally, it has been used for acute cerebral infarction relief as well as other pharmacological actions. However, heparin's self-aggregated macrocomplex may reduce blood circulation time and induce life-threatening thrombocytopenia (HIT) complicating the use of heparins. Nonetheless, the conjugation of heparin to immuno-stealth biomolecules may overcome these obstacles. An immunostealth recombinant viral capsid protein (VP28) was expressed and conjugated with heparin to form a novel nanoparticle (VP28-heparin). VP28-heparin was characterized and tested to determine its immunogenicity, anticoagulation properties, effects on total platelet count, and risk of inducing HIT in animal models. The synthesized VP28-heparin trimeric nanoparticle was non-immunogenic, possessed an average hydrodynamic size (8.81 ± 0.58 nm) optimal for the evasion renal filtration and reticuloendothelial system uptake (hence prolonging circulating half-life). Additionally, VP28-heparin did not induce mouse death or reduce blood platelet count when administered at a high dosein vivo(hence reducing HIT risks). The VP28-heparin nanoparticle also exhibited superior anticoagulation properties (2.2× higher prothrombin time) and comparable activated partial thromboplastin time, but longer anticoagulation period when compared to unfractionated heparin. The anticoagulative effects of the VP28-heparin can also be reversed using protamine sulfate. Thus, VP28-heparin may be an effective and safe heparin derivative for therapeutic use.
Asunto(s)
Heparina , Trombocitopenia , Animales , Ratones , Heparina/farmacología , Heparina/uso terapéutico , Anticoagulantes/farmacología , Coagulación Sanguínea , Trombocitopenia/tratamiento farmacológico , Recuento de PlaquetasRESUMEN
The expansion dynamics of air plasma induced by 1,064 nm nanosecond laser pulse was studied by plasma fluorescence method. The time evolution images of air plasma expansion were acquired using the ICCD camera at different laser pulse energy, and the expansion velocity of air plasma was deduced based on the air plasma frontier expansion wave front distance at 150 mJ. The experimental results show that the plasma fluorescence was mainly distributed in the plasma expansion region, the plasma fluorescence intensity firstly increased then became weaker and the expansion area increased gradually with time evolution. The biggest expansion distance was 3. 76 mm with 300 mi at 20 ns. The plasma expansion speed was the order of magnitude of 10s m · s(-1) at the early stage of expansion process. The expansion speed of air plasma decayed rapidly within 16ns, then changed slowly with time. The time of air breakdown was close to the rising phase of laser pulse when the greater laser pulse energy was radiated.