Oral bioavailability of a low molecular weight heparin using a polymeric delivery system
Oral bioavailability of a low molecular weight heparin using a polymeric delivery system
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DOI：
10.1016/j.jconrel.2006.03.020
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发表时间：
2006-06-12
影响因子：
10.8
通讯作者：
Ubrich, Nathalie
中科院分区：
文献类型：
--
作者：
Hoffart, Valerie;Lamprecht, Alf;Ubrich, Nathalie
低分子量肝素（LMWH）是预防关节成形术和腹部手术患者深静脉血栓形成（DVT）的标准抗凝剂。然而，迄今为止，LMWH仅通过肠胃外途径施用。因此，在门诊治疗中，它们通常被口服华法林替代。由于华法林起效缓慢，药物间相互作用发生率高，因此非常需要开发口服LMWH制剂。通过复乳法制备的聚酯和聚阳离子聚甲基丙烯酸酯共混物负载的LMWH（亭扎肝素）纳米粒在禁食家兔中口服给药。通过显色抗Xa因子测定法测定血浆亭扎肝素浓度。口服两种剂量的亭扎肝素纳米粒（200和600 anti-Xa U/kg）后，在4至10或12 h之间观察到口服吸收，延迟起效时间为3至4 h。两种试验剂量的平均绝对生物利用度分别为51%和59%。我们现在报道，将汀扎肝素封装到纳米粒中可能有助于其口服疗效，其抗凝作用延长至8小时。(c)2006 Elsevier B. V.保留所有权利。
Low molecular weight heparins (LMWHs) are the standards of anticoagulant for the prevention of deep vein thrombosis (DVT) in patients undergoing arthroplasty and abdominal surgery. However, LMWHs are so far only administered by parenteral route. Thus, they are usually replaced by oral warfarin for outpatient therapy. Since warfarin has a slow onset and high incidence of drug-drug interaction, there is a great need for the development of an oral LMWH formulation. LMWH (tinzaparin)-loaded nanoparticles prepared with a blend of a polyester and a polycationic polymethacrylate by the double emulsion method were administered orally in fasted rabbits. The plasma tinzaparin concentration was measured by a chromogenic anti-factor Xa assay. After oral administration of two doses of tinzaparin-loaded nanoparticles (200 and 600 anti-Xa U/kg), the oral absorption was observed between 4 and 10 or 12 h, with a delayed onset of action ranging from 3 to 4 h. Mean absolute bioavailabilities were 51% and 59% for the two tested doses. We now report that the encapsulation of tinzaparin into nanoparticles is likely to contribute to its oral efficacy with an anticoagulant effect prolonged up to 8 h. (c) 2006 Elsevier B.V. All rights reserved.