Therapeutic impact of erythropoietin-encapsulated liposomes targeted to bone marrow on renal anemia.
Therapeutic impact of erythropoietin-encapsulated liposomes targeted to bone marrow on renal anemia.
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靶向骨髓的促红细胞生成素封装脂质体对肾性贫血的治疗作用。
DOI：
10.1021/mp500453a
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Maruyama T.
中科院分区：
文献类型：
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作者：
Miyazaki Y;Taguchi K;Sou K;Watanabe H;Ishima Y;Miyakawa T;Mitsuya H, Fukagawa M;Otagiri M;Maruyama T.
骨髓是诊断红细胞生成障碍（包括贫血）的关键要素，也是其治疗的潜在目标。然而，由于将诊断剂和治疗剂有效地递送至骨髓是困难的，所以这种递送是通过大量施用通常具有不良作用的药物来实现的。在这里，我们通过将重组人促红细胞生成素（rHuEPO）封装在具有l-谷氨酸，N-（3-羧基-1-氧代丙基）-，1,5-二十六烷基酯（SA）（脂质体-EPO）的脂质体中，实现了将重组人促红细胞生成素（rHuEPO）选择性递送至骨髓。在肾性贫血兔模型中，结果显示对造血有有益作用，比单独使用 rHuEPO 更好。此外，我们还确定，由于 SA 的存在，脂质体-EPO 向骨髓的递送取决于骨髓巨噬细胞的特异性摄取。这些结果表明，脂质体-EPO是一种新的、有前途的促红细胞生成素刺激剂，并且含有SA的脂质体具有在源自骨髓的疾病的诊断和治疗应用中的潜力。
Bone marrow is a key element in the diagnosis of disorders of erythropoiesis, including anemia, and a potential target in their treatment. However, because efficient delivery of diagnostic and therapeutic agents to bone marrow is difficult, such delivery is achieved by administering drugs in large quantities that often have adverse effects. Here, we achieved selective delivery of recombinant human erythropoietin (rHuEPO) to bone marrow, via its encapsulation in liposomes withl-glutamic acid,N-(3-carboxy-1-oxopropyl)-, 1,5-dihexadecyl ester (SA) (liposome-EPO). The result, in a rabbit model of renal anemia, was a beneficial effect on hematopoiesis, better than with rHuEPO alone. Also, we determined that liposome-EPO delivery to bone marrow depended on specific uptake by bone marrow macrophages because of the presence of SA. These results indicate both that liposome-EPO is a new, promising erythropoietin-stimulating agent and that liposomes with SA have potential for diagnostic and therapeutic applications in diseases originating from bone marrow.