PubMed · 14194076
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A CATTAN. [THE THROMBOTEST].. https://pubmed.ncbi.nlm.nih.gov/14194076/
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Zein was studied as a drug-eluting coating film composed of zein microspheres for cardiovascular devices (e.g. stent). In vitro 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) analysis showed that both zein film and its degraded product had better biocompatibility compared with Corning culture plate on the growth of human umbilical veins endothelial cells (HUVECs, p<0.05, n=6), and the effect of zein degraded product on HUVECs was dose-dependent. The best result was obtained at 0.3 mg/ml of the addition. The encapsulation efficiency of heparin and heparin loading varied with the amount of both zein and heparin, and the highest encapsulation efficiency (heparin 1.33 mg/ml and zein 16 mg/ml) was 22.77+/-1.33% (n=3). Scanning electron microscope (SEM) observation indicated that the zein film was made of microspheres in diameter from nano- to micrometer, which could be controlled. Sizes of heparin-loaded zein microspheres changed before and after release of heparin because of conglutination among zein microspheres. Release rate of heparin from microsphere film reached to 33.5+/-1.2% within 12 h, and began to get into subsequent "slow release" phase; about 55% of the entrapped heparin was released after 20 days. Both zein film and heparin-loaded zein microsphere film were effective in suppressing platelet adhesion, and the heparin-loaded film showed a better anticoagulation as determined with thrombin time (TT) assay. These results suggest that zein film could be used directly as a new type of coating material for its better biocompatibility with HUVECs. Moreover, the heparin-loaded zein microsphere film can significantly improve the hemocompatibility.
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The journey towards a detailed mechanistic understanding of the anticoagulant action of heparin has resulted in synthetic mimetics with improved pharmacodynamic profiles. Inspired by the ternary complex formation of heparin with antithrombin III and thrombin, the active pentasaccharide fondaparinux has been succeeded by several clinical candidates, such as SR123781, that have tailor-made factor Xa and thrombin inhibitory activities combined with less aspecific binding (e.g. binding to platelet factor 4 involved in thrombocytopenia). Novel compounds with both antithrombin III-mediated inhibition of factor Xa and direct thrombin inhibition are emerging. Org42675 is one such compound, balancing dual inhibition of factor Xa and thrombin in one anticoagulant drug, with excellent pharmacokinetic properties and strong inhibitory activity toward clot-bound thrombin.