Yu Lu, Gao Yanguang, Yue Xiuli, Liu Shaoqin, Dai Zhifei
Nanomedicine and Biosensor Laboratory, Bio-X Center, Harbin Institute of Technology, Harbin 150080, China.
Langmuir. 2008 Dec 2;24(23):13723-9. doi: 10.1021/la802611b.
Iron-polysaccharide complex have been extensively utilized in the treatment of iron deficiency anemia for parenteral administration. Herein, a novel iron-heparin complexed hollow capsules with nanoscaled wall thickness have been fabricated by means of alternating deposition of ferric ions (III) (Fe+) and heparin (Hep) onto the surface of submicroscaled (488 nm) and microscaled (10.55 microm) polystyrene latex particles via both electrostatic interaction and chemical complexation processes, followed by dissolution of the cores using tetrahydrofuran. Confocal micrographs and atomic force microscopy (AFM) images prove that iron-heparin complexed submicroscaled hollow capsules keep spherical shapes in solution and even after drying. The activated partial thromboplastin time (APTT) assay shows that complexing with ferric ions do not compromise the catalytic capacity of heparin to promote antithrombin III-mediated thrombin inactivation. The anticoagulant activity value of (Fe3+/Hep)8 capsules is evaluated to be about 95.7 U/mg, indicating that approximately 0.55 mg heparin was in 1 mg powder of submicroscaled (Fe3+/Hep)8 hollow capsules. Compared with the same dosage of heparin, iron-heparin complexed hollow capsules display a more prolonged anticoagulant duration than heparin. All these results reveal that such submicroscaled iron-heparin complexed hollow capsules have application potential as an injectable anticoagulant vehicle.
铁多糖复合物已被广泛用于缺铁性贫血的肠胃外给药治疗。在此，通过三价铁离子（Fe³⁺）和肝素（Hep）经由静电相互作用和化学络合过程交替沉积在亚微米级（488 nm）和微米级（10.55 微米）聚苯乙烯乳胶颗粒表面，随后用四氢呋喃溶解内核，制备出了一种具有纳米级壁厚的新型铁 - 肝素复合空心胶囊。共聚焦显微镜图像和原子力显微镜（AFM）图像证明，铁 - 肝素复合亚微米级空心胶囊在溶液中甚至干燥后都保持球形。活化部分凝血活酶时间（APTT）测定表明，与铁离子络合不会损害肝素促进抗凝血酶 III 介导的凝血酶失活的催化能力。（Fe³⁺/Hep）₈胶囊的抗凝血活性值经评估约为 95.7 U/mg，表明在 1 mg 亚微米级（Fe³⁺/Hep）₈空心胶囊粉末中约含有 0.55 mg 肝素。与相同剂量的肝素相比，铁 - 肝素复合空心胶囊的抗凝血持续时间比肝素更长。所有这些结果表明，这种亚微米级铁 - 肝素复合空心胶囊作为可注射抗凝血载体具有应用潜力。
