Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, Ontario, N6A 5B9, Canada.
Curr Drug Deliv. 2011 Mar;8(2):164-71. doi: 10.2174/156720111794479862.
Recombinant human erythropoietin (rHu-EPO) is a glycoprotein, which is produced commercially from Chinese hamster ovary (CHO) cells. It is used for the therapy of renal anemia and chemotherapy-induced anemia in cancer patients. Recent evidence suggests that rHu-EPO exerts tissue protective effects via multiple mechanisms which include inhibition of apoptosis, promotion of angiogenesis and decreased inflammation. After intravenous (i.v.) injection, the blood concentration of rHu-EPO rapidly decreases due to proteolysis resulting in a relatively short half-life of 8.5 h, which necessitates regular dosing with intervals that do not exceed 7 days. It would be desirable to develop an encapsulated formulation providing controlled release of rHu-EPO to maintain therapeutic concentrations in plasma, and for potential tissue protective applications to maintain high local therapeutic concentrations in tissue while minimizing potential unwanted systemic effects such as polycythemia and platelet activation, both of which can predispose to intravascular thrombosis. Nanoparticle encapsulation of rHu-EPO can also allow for direct injection at sites of injury in specific tissues/organs, again minimizing systemic exposure of the drug. In this paper, we report the production of biopolymer nanoparticles by ionotropic gelation of chitosan with tripolyphosphate (TPP). The nanoparticle size distribution in aqueous solution was determined and rates of rHu-EPO release from chitosan-TPP nanoparticles were measured in PBS at 37°C. It was observed that almost 30% of the encapsulated rHu-EPO was released within the first 48 hours and thereafter a linear release profile was observed for up to 2 weeks. Total drug release over 15 days was 63% of the initial amount.
重组人促红细胞生成素（rHu-EPO）是一种糖蛋白，它是通过中国仓鼠卵巢（CHO）细胞商业化生产的。它用于治疗肾性贫血和癌症患者的化疗诱导性贫血。最近的证据表明，rHu-EPO 通过多种机制发挥组织保护作用，包括抑制细胞凋亡、促进血管生成和减少炎症。静脉注射（i.v.）后，rHu-EPO 的血液浓度因蛋白水解而迅速下降，导致半衰期相对较短，仅为 8.5 小时，这需要定期给药，间隔不超过 7 天。开发一种封装制剂，提供 rHu-EPO 的控释，以维持血浆中的治疗浓度，并用于潜在的组织保护应用，以维持组织中的高局部治疗浓度，同时最大限度地减少潜在的全身不良影响，如红细胞增多症和血小板激活，这两者都可能导致血管内血栓形成。rHu-EPO 的纳米颗粒包封也可以允许在特定组织/器官的损伤部位直接注射，再次最大限度地减少药物的全身暴露。在本文中，我们报告了通过壳聚糖与三聚磷酸（TPP）的离子凝胶化生产生物聚合物纳米颗粒。在水溶液中测定了纳米颗粒的粒径分布，并在 37°C 的 PBS 中测量了 rHu-EPO 从壳聚糖-TPP 纳米颗粒中的释放速率。观察到，在最初的 48 小时内，几乎 30%的包裹 rHu-EPO 被释放出来，此后观察到长达 2 周的线性释放曲线。在 15 天内，总药物释放量为初始量的 63%。
