Pharmaceutical Strategies Utilizing Recombinant Human Serum Albumin
Pharmaceutical Strategies Utilizing Recombinant Human Serum Albumin
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DOI：
10.1023/a:1015396825274
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发表时间：
2002-05
影响因子：
3.7
通讯作者：
Victor Tuan Giam Chuang;U. Kragh‐Hansen;M. Otagiri
中科院分区：
文献类型：
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作者：
Victor Tuan Giam Chuang;U. Kragh‐Hansen;M. Otagiri
基因操作技术开辟了制备具有理想治疗特性的重组人血清白蛋白（rHSA）或突变体以及蛋白融合产物的可能性。rHSA可以作为合成血红素蛋白的载体，从而可逆地携带氧。胰岛素的肉豆蔻酰化由于自身聚集和白蛋白结合增加而导致半衰期延长。肿瘤细胞对白蛋白的优先摄取是白蛋白-抗癌药物偶联物制剂的基础。此外，药物靶向可以通过将药物掺入白蛋白微球中来实现，而肝靶向可以通过将药物与半乳糖基化或甘露糖基化白蛋白缀合来实现。不同尺寸的微球和纳米颗粒可以在有或没有药物和/或放射性同位素的情况下用于药物递送或诊断目的。与大鼠类器官相比，在体内植入包封在HSA-藻酸盐包被的珠粒中的白蛋白融合蛋白表达细胞显示出有希望的结果。以阳离子化白蛋白为转运体的嵌合肽策略可以通过受体介导的胞吞转运作用将药物传递通过血脑屏障。含基因的白蛋白微泡超声造影剂在超声破坏后可无创性地传递基因。HSA的各种定点突变体可以根据所需的应用而定制。
Gene manipulation techniques open up the possibility of making recombinant human serum albumin (rHSA) or mutants with desirable therapeutic properties and for protein fusion products. rHSA can serve as a carrier in synthetic heme protein, thus reversibly carrying oxygen. Myristoylation of insulin results in a prolonged half-life because of self aggregation and increased albumin binding. Preferential albumin uptake by tumor cells serves as the basis for albumin-anticancer drug conjugate formulation. Furthermore, drug targeting can be achieved by incorporating drugs into albumin microspheres whereas liver targeting can be achieved by conjugating drug with galactosylated or mannosylated albumin. Microspheres and nanoparticles of different sizes can, with or without drugs and/or radioisotopes, be used for drug delivery or diagnostic purposes.In vivoimplantation of albumin fusion protein expressing cells encapsulated in HSA-alginate coated beads showed promising results compared to organoids in rats. Chimeric peptide strategy with cationized albumin as the transport can deliver drugs via receptor mediated transcytosis through the blood brain barrier. Gene bearing, albumin microbubbles containing ultrasound contrast agents can non-invasively deliver gene after destruction by ultrasound. Various site-directed mutants of HSA can be tailor made depending on the application required.