製備與評估以多孔鐵粒子作為口服鐵劑之研究

Abstract

失血是導致與透析有關的鐵缺乏症的主要因素，長期失血將導致缺鐵性貧血。 對於許多患者來說，口服鐵劑是一線治療。元素鐵是一種100% 鐵質來源，可減少每日服藥次數。本研究利用合成的多孔性鐵粒子（Porous Iron Particle, PIP）用於治療缺鐵性貧血的病患。使用改良的硼氫化物還原法成功地合成了多孔鐵顆粒。該方法能夠顯著提高孔徑和表面積，從而增加溶解度。通過Caco-2 細胞模型體外測量其生物利用度，通過監測Caco-2細胞中鐵蛋白的含量來檢查多孔性鐵粒子的體外生物利用度。由於多孔性鐵粒子孔徑提高增加其表面，造成PIP 的鐵蛋白吸收量明顯高於多孔性較差的商業鐵顆粒( p<0.05)。在缺鐵性貧血大鼠中的生物利用度相比，通過測量體重與血紅素相關的參數來檢查多孔性鐵粒子的體內生物利用度。最後，與長期貧血對照組相比，補充多孔性鐵粒子的貧血大鼠的平均血紅蛋白含量和血紅蛋白再生效率明顯更高(p<0.01)。因此，在缺鐵性貧血中，多孔性鐵粒子可以有效恢復血紅素。在為期兩周的口服毒性試驗中，多孔性鐵粒子對大鼠生理學及組織病理學無明顯毒性且不會造成肝臟毒性。因此，在缺鐵性貧血中多孔性鐵粒子可以有效恢復血紅素。

Blood loss is the main factor leading to iron deficiency related to hemodialysis. Long-term blood loss will lead to iron deficiency anemia. For many patients, oral iron is the first-line treatment. Elemental iron is a 100% iron source that reduces the number of daily medications. In this study, synthetic porous iron particles (PIP) were used to treat patients with iron deficiency anemia. Porous iron particles were successfully synthesized using a modified borohydride reduction method. This method can significantly increase pore size and surface area, thereby increasing solubility. The bioavailability of Caco-2 cell model was measured in vitro, and the in vitro bioavailability of porous iron particles was checked by monitoring the content of ferritin in Caco-2 cells. As the pore size of the porous iron particles increases and the surface is increased, the ferritin absorption of PIP is significantly higher than that of commercial iron particles with poor porosity (p<0.05). Compared with the bioavailability in iron-deficiency anemia rats, the in vivo bioavailability of porous iron particles was examined by measuring the parameters related to body weight and hemoglobin. Finally, compared with the anemia control group, the average hemoglobin content and hemoglobin regeneration efficiency of anemia rats supplemented with porous iron particles were significantly higher (p<0.01). Therefore, in iron-deficiency anemia, porous iron particles can effectively restore hemoglobin. In the two-week oral toxicity test, porous iron particles were not significantly toxic to rat physiology and histopathology and did not cause liver toxicity. Therefore, porous iron particles can effectively restore hemoglobin in iron-deficiency anemia.