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Pharmaceutical Strategies Utilizing Recombinant Human Serum Albumin

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Abstract

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 vivo implantation 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.

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REFERENCES

  1. T. Peters, Jr. All about albumin: biochemistry, genetics, and medical applications, Academic Press, San Diego, California 1996.

    Google Scholar 

  2. J. Iglesias, V. E. Abernethy, Z. Wang, W. Lieberthal, J. S. Koh, and J. S. Levine. Albumin is a major serum survival factor for renal tubular cells and macrophages through scavenging of ROS. Am.J.Physiol. 277:F711–722 (1999).

    Google Scholar 

  3. M. L. Wratten, L. Sereni, and C. Tetta. Oxidation of albumin is enhanced in the presence of uremic toxins. Ren.Fail. 23:563–571 (2001).

    Google Scholar 

  4. E. Tarelli, A. Mire-Sluis, H. A. Tivnann, B. Bolgiano, D. T. Crane, C. Gee, X. Lemercinier, M. L. Athayde, N. Sutcliffe, P. H. Corran, and B. Rafferty. Recombinant human albumin as a stabilizer for biologic materials and for the preparation of international reference reagents. Biologicals 26:331–346 (1998).

    Google Scholar 

  5. G. Gellissen and C. P. Hollenberg. Application of yeasts in gene expression studies: a comparison of Saccharomyces cerevisiae, Hansenula polymorpha and Kluyveromyces lactis-a review. Gene 190:87–97 (1997).

    Google Scholar 

  6. S. M. Kingsman, D. Cousens, C. A. Stanway, A. Chambers, M. Wilson, and A. J. Kingsman. High-efficiency yeast expression vectors based on the promoter of the phosphoglycerate kinase gene. Methods Enzymol. 185:329–341 (1990).

    Google Scholar 

  7. D. Sleep, J. E. Ogden, N. A. Roberts, and A. R. Goodey. Cloning and characterisation of the Saccharomyces cerevisiae glycerol-3-phosphate dehydrogenase (GUT2) promoter. Gene 101:89–96 (1991).

    Google Scholar 

  8. N. Nomura, N. Matsubara, S. Horinouchi, and T. Beppu. Secretion by Saccharomyces cerevisiae of human apolipoprotein E as a fusion to serum albumin. Biosci.Biotechnol.Biochem. 59:532–534 (1995).

    Google Scholar 

  9. S. M. Kerry-Williams, S. C. Gilbert, L. R. Evans, and D. J. Ballance. Disruption of the Saccharomyces cerevisiae YAP3 gene reduces the proteolytic degradation of secreted recombinant human albumin. Yeast 14:161–169 (1998).

    Google Scholar 

  10. R. Fleer, P. Yeh, N. Amellal, I. Maury, A. Fournier, F. Bacchetta, P. Baduel, G. Jung, H. L'Hote, J. Becquart, H. Fukuhara, and J. F. Mayaux. Stable multicopy vectors for high-level secretion of recombinant human serum albumin by Kluyveromyces yeasts. Biotechnology (NY) 9:968–975 (1991).

    Google Scholar 

  11. M. Saliola, C. Mazzoni, N. Solimando, A. Crisa, C. Falcone, G. Jung, and R. Fleer. Use of the KlADH4 promoter for ethanoldependent production of recombinant human serum albumin in Kluyveromyces lactis. Appl.Environ.Microbiol. 65:53–60 (1999).

    Google Scholar 

  12. W. G. Bao and H. Fukuhara. Secretion of human proteins from yeast: stimulation by duplication of polyubiquitin and protein disulfide isomerase genes in Kluyveromyces lactis. Gene 272:103–110 (2001).

    Google Scholar 

  13. J. M. Cregg, J. L. Cereghino, J. Shi, and D. R. Higgins. Recombinant protein expression in Pichia pastoris. Mol.Biotechnol. 16: 23–52 (2000).

    Google Scholar 

  14. J. L. Cereghino and J. M. Cregg. Heterologous protein expression in the methylotrophic yeast Pichia pastoris. FEMS Microbiol.Rev. 24:45–66 (2000).

    Google Scholar 

  15. H. Ohi, M. Miura, R. Hiramatsu, and T. Ohmura. The positive and negative cis-acting elements for methanol regulation in the Pichia pastoris AOX2 gene. Mol.Gen.Genet. 243:489–499 (1994).

    Google Scholar 

  16. H. A. Kang, W. Kang, W. K. Hong, M. W. Kim, J. Y. Kim, J. H. Sohn, E. S. Choi, K. B. Choe, and S. K. Rhee. Development of expression systems for the production of recombinant human serum albumin using the MOX promoter in Hansenula polymorpha DL-1. Biotechnol.Bioeng. 76:175–185 (2001).

    Google Scholar 

  17. C. E. Petersen, C.-E. Ha, D. M. Jameson, and N. V. Bhagavan. Mutations in a specific human serum albumin thyroxine binding site define the structural basis of familial dysalbuminemic hyperthyroxinemia. J.Biol.Chem. 271:19110–19117 (1996).

    Google Scholar 

  18. C. E. Petersen, C.-E. Ha, K. Harohalli, D. S. Park, J. B. Feix, O. Isozaki, and N. V. Bhagavan. Structural investigations of a new familial dysalbuminemic hyperthyroxinemia genotype. Clin.Chem. 45:1248–1254 (1999).

    Google Scholar 

  19. K. Kobayashi. Development of recombinant human serum albumin. In M. Otagiri, Y. Sugiyama, B. Testa, and J. P. Tillement (eds.), Proceedings of the International Symposium on Serum Albumin & α 1 -Acid Glycoprotein, Kumamoto, Japan 2001 pp. 321–329

  20. H. Watanabe, S. Tanase, K. Nakajou, T. Maruyama, U. Kragh-Hansen, and M. Otagiri. Role of Arg-410 and Tyr-411 in human serum albumin for ligand binding and esterase-like activity. Biochem.J. 349:813–819 (2000).

    Google Scholar 

  21. H. Watanabe, U. Kragh-Hansen, S. Tanase, K. Nakajou, M. Mitarai, Y. Iwao, T. Maruyama, and M. Otagiri. Conformational stability and warfarin-binding properties of human serum albumin studied by recombinant mutants. Biochem.J. 357:269–274 (2001).

    Google Scholar 

  22. H. Watanabe, K. Yamasaki, U. Kragh-Hansen, S. Tanase, K. Harada, A. Suenaga, and M. Otagiri. In vitro and in vivo properties of recombinant human serum albumin from pichia pastoris purified by a method of short processing time. Pharm.Res. 18: 1775–1781 (2001).

    Google Scholar 

  23. S. Sugio, A. Kashima, S. Mochizuki, M. Noda, and K. Kobayashi. Crystal structure of human serum albumin at 2.5 Å resolution. Protein Eng. 12:439–446 (1999).

    Google Scholar 

  24. T. Komatsu, E. Tsuchida, and K. Kobayashi. Oxygen-transport albumin: A new hemoprotein incorporating lipidhemes as a red cell substitute. In E. Tsuchida (ed.), Blood Substitutes: Present and Future Perspectives, Elsevier, The Netherlands, 1998 pp. 315–326.

    Google Scholar 

  25. E. Tsuchida. An oxygen infusion: Conjugate of human serum albumin-heme as O2-carrying system. In M. Otagiri, Y. Sugiyama, B. Testa and J.P. Tillement (eds.), Proceedings of the International Symposium on Serum Albumin & α 1 -Acid Glycorprotein, Kumamoto, Japan 2001 pp. 311–320.

  26. E. Tsuchida, T. Komatsu, Y. Matsukawa, K. Hamamatsu, and J. Wu. Human serum albumin incorporating Tetrakis(opivalamido) phenylporphinatoiron(II) derivative as a totally synthetic O2-carrying hemoprotein. Bioconjug.Chem. 10:797–802 (1999).

    Google Scholar 

  27. T. Komatsu, K. Hamamatsu, S. Takeoka, H. Nishide, and E. Tsuchida. Human serum albumin-bound synthetic hemes as an oxygen carrier: determination of equilibrium constants for heme binding to host albumin. Artif.Cells Blood Substit.Immobil.Biotechnol. 26:519–527 (1998).

    Google Scholar 

  28. T. Komatsu, K. Hamamatsu, J. Wu, and E. Tsuchida. Physicochemical properties and O2-coordination structure of human serum albumin incorporating tetrakis(o-pivalamido)phenylporphyrinatoiron( II) derivatives. Bioconjug.Chem. 10:82–86 (1999).

    Google Scholar 

  29. E. Tsuchida, T. Komatsu, K. Hamamatsu, Y. Matsukawa, A. Tajima, A. Yoshizu, Y. Izumi, and K. Kobayashi. Exchange transfusion with albumin-heme as an artificial O2-infusion into anesthetized rats: physiological responses, O2-delivery, and reduction of the oxidized hemin sites by red blood cells. Bioconjug.Chem. 11:46–50 (2000).

    Google Scholar 

  30. J. Markussen, S. Havelund, I. Jonassen, T. B. Kjeldsen, U. Ribel, P. Kurtzhals, and M. Hamilton-Wessler. Albumin binding of insulins acylated with fatty acids and other hydrophobic moieties. In M. Otagiri, Y. Sugiyama, B. Testa and J.P. Tillement (eds.), Proceedings of the International Symposium on Serum Albumin & α 1 1-Acid Glycorprotein, Kumamoto, Japan 2001 pp. 299–310.

  31. P. Kurtzhals, S. Havelund, I. Jonassen, B. Kiehr, U. D. Larsen, U. Ribel, and J. Markussen. Albumin binding of insulins acylated with fatty acids: characterization of the ligand-protein interaction and correlation between binding affinity and timing of the insulin effect in vivo. Biochem.J. 312:725–731 (1995).

    Google Scholar 

  32. M. Hamilton-Wessler, M. Ader, M. Dea, D. Moore, P. N. Jorgensen, J. Markussen, and R. N. Bergman. Mechanism of protracted metabolic effects of fatty acid acylated insulin, NN304, in dogs: retention of NN304 by albumin. Diabetologia 42:1254–1263 (1999).

    Google Scholar 

  33. G. A. Brunner, G. Sendhofer, A. Wutte, M. Ellmerer, B. Sogaard, A. Siebenhofer, S. Hirschberger, G. J. Krejs, and T. R. Pieber. Pharmacokinetic and pharmacodynamic properties of long-acting insulin analogue NN304 in comparison to NPH insulin in humans. Exp.Clin.Endocrinol.Diabetes 108:100–105 (2000).

    Google Scholar 

  34. K. Hermansen, S. Madsbad, H. Perrild, A. Kristensen, and M. Axelsen. Comparison of the soluble basal insulin analog insulin detemir with NPH insulin: a randomized open crossover trial in type 1 diabetic subjects on basal-bolus therapy. Diabetes Care 24:296–301 (2001).

    Google Scholar 

  35. G. M. Kindberg, H. Tolleshaug, and T. Skotland. Uptake and degradation of radioactively labeled albumin microspheres as markers for Kupffer cell phagocytosis. Cell Tissue Res. 300:397–400 (2000).

    Google Scholar 

  36. N. Watanabe, N. Oriuchi, K. Endo, T. Inoue, S. Tanada, H. Murata, and Y. Sasaki. Yttrium-90-labeled human macroaggregated albumin for internal radiotherapy: combined use with DTPA. Nucl.Med.Biol. 26:847–851 (1999).

    Google Scholar 

  37. G. Wunderlich, J. Pinkert, M. Andreeff, M. Stintz, F. F. Knapp, Jr., J. Kropp, and W. G. Franke. Preparation and biodistribution of rhenium-188 labeled albumin microspheres B 20: a promising new agent for radiotherapy. Appl.Radiat.Isot. 52:63–68 (2000).

    Google Scholar 

  38. A. C. Perkins and M. Frier. Experimental biodistribution studies of 99mTc-recombinant human serum albumin (rHSA): a new generation of radiopharmaceutical. Eur.J.Nucl.Med. 21:1231–1233 (1994).

    Google Scholar 

  39. Y. Nishiyama, Y. Yamamoto, Y. Mori, K. Satoh, H. Takashima, M. Ohkawa, and M. Tanabe. Usefulness of Technetium-99m human serum albumin lymphoscintigraphy in chyluria. Clin.Nucl.Med. 23:429–431 (1998).

    Google Scholar 

  40. I. Bedrosian, A. M. Scheff, R. Mick, L. S. Callans, L. P. Bucky, F. R. Spitz, C. Helsabeck, D. E. Elder, A. Alavi, D. F. Fraker, and B. J. Czerniecki. 99mTc-human serum albumin: an effective radiotracer radiotracer for identifying sentinel lymph nodes in melanoma. J.Nucl.Med. 40:1143–1148 (1999).

    Google Scholar 

  41. T. Rink, T. Heuser, H. Fitz, H. J. Schroth, E. Weller, and H. H. Zippel. Lymphoscintigraphic sentinel node imaging and gamma probe detection in breast cancer with Tc-99m nanocolloidal albumin: results of an optimized protocol. Clin.Nucl.Med. 26:293–298 (2001).

    Google Scholar 

  42. N. T. Chiu, B. F. Lee, S. J. Hwang, J. M. Chang, and G. C. Liu. and H. S. Yu. Protein-losing enteropathy: diagnosis with (99m)Tc-labeled human serum albumin scintigraphy. Radiology 219:86–90 (2001).

    Google Scholar 

  43. K. Suga, N. Kume, N. Matsunaga, K. Motoyama, A. Hara, and N. Ogasawara. Assessment of leg oedema by dynamic lymphoscintigraphy with intradermal injection of technetium-99m human serum albumin and load produced by standing. Eur.J.Nucl.Med. 28:294–303 (2001).

    Google Scholar 

  44. K. Ogawara, M. Nishikawa, Y. Takakura, and M. Hashida. Pharmacokinetic analysis of hepatic uptake of galactosylated bovine serum albumin in a perfused rat liver. J.Control.Release 50:309–317 (1998).

    Google Scholar 

  45. K. Ogawara, S. Hasegawa, M. Nishikawa, Y. Takakura, and M. Hashida. Pharmacokinetic evaluation of mannosylated bovine serum albumin as a liver cell-specific carrier: quantitative comparison with other hepatotropic ligands. J.Drug Target. 6:349–360 (1999).

    Google Scholar 

  46. L. Beljaars, G. Molema, B. Weert, H. Bonnema, P. Olinga, G. M. Groothuis, D. K. Meijer, and K. Poelstra. Albumin modified with mannose 6-phosphate: A potential carrier for selective delivery of antifibrotic drugs to rat and human hepatic stellate cells. Hepatology 29:1486–1493 (1999).

    Google Scholar 

  47. J. H. Han, Y. K. Oh, D. S. Kim, and C. K. Kim. Enhanced hepatocyte uptake and liver targeting of methotrexate using galactosylated albumin as a carrier. Int.J.Pharm. 188:39–47 (1999).

    Google Scholar 

  48. L. Beljaars, G. Molema, B. Weert, H. Bonnema, P. Olinga, G. M. Groothuis, D. K. Meijer, and K. Poelstra. Albumin modified with mannose 6-phosphate: A potential carrier for selective delivery of antifibrotic drugs to rat and human hepatic stellate cells. Hepatology 29:1486–1493 (1999).

    Google Scholar 

  49. L. Beljaars, G. Molema, D. Schuppan, A. Geerts, P. J. De Bleser, B. Weert, D. K. Meijer, and K. Poelstra. Successful targeting to rat hepatic stellate cells using albumin modified with cyclic peptides that recognize the collagen type VI receptor. J.Biol.Chem. 275:12743–12751 (2000).

    Google Scholar 

  50. D. K. Meijer, L. Beljaars, G. Molema, and K. Poelstra. Diseaseinduced drug targeting using novel peptide-ligand albumins. J.Control.Release 72:157–164 (2001).

    Google Scholar 

  51. A. H. Kwon, Y. Matsui, S. K. Ha-Kawa, and Y. Kamiyama. Functional hepatic volume measured by technetium-99m-galactosylhuman serum albumin liver scintigraphy: comparison between hepatocyte volume and liver volume by computed tomography. Am.J.Gastroenterol. 96:541–546 (2001).

    Google Scholar 

  52. N. Sasaki, S. Shiomi, Y. Iwata, S. Nishiguchi, T. Kuroki, J. Kawabe, and H. Ochi. Clinical usefulness of scintigraphy with 99mTc-galactosyl-human serum albumin for prognosis of cirrhosis of the liver. J.Nucl.Med. 40:1652–1656 (1999).

    Google Scholar 

  53. G. Stehle, A. Wunder, H. H. Schrenk, G. Hartung, D. L. Heene, and H. Sinn. Albumin-based drug carriers: comparison between serum albumins of different species on pharmacokinetics and tumor uptake of the conjugate. Anticancer Drugs 10:785–790 (1999).

    Google Scholar 

  54. F. Kratz, R. Muller-Driver, I. Hofmann, J. Drevs, and C. Unger. A novel macromolecular prodrug concept exploiting endogenous serum albumin as a drug carrier for cancer chemotherapy. J.Med.Chem. 43:1253–1256 (2000).

    Google Scholar 

  55. H. Maeda, J. Wu, T. Sawa, Y. Matsumura, and K. Hori. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J.Control.Release 65:271–284 (2000).

    Google Scholar 

  56. Y. Takakura, T. Fujita, M. Hashida, and H. Sezaki. Diposition characteristics of macromolecules in tumor-bearing mice. Pharm.Res. 7:339–346 (1990).

    Google Scholar 

  57. G. Stehle, H. Sinn, A. Wunder, H. H. Schrenk, S. Schutt, W. Maier-Borst, and D. L. Heene. The loading rate determines tumor targeting properties of methotrexate-albumin conjugates in rats. Anticancer Drugs 8:677–685 (1997).

    Google Scholar 

  58. G. Hartung, G. Stehle, H. Sinn, A. Wunder, H. H. Schrenk, S. Heeger, M. Kranzle, L. Edler, E. Frei, H. H. Fiebig, D. L. Heene, W. Maier-Borst, and W. Queisser. Phase I trial of methotrexatealbumin in a weekly intravenous bolus regimen in cancer patients. Phase I Study Group of the Association for Medical Oncology of the German Cancer Society. Clin.Cancer Res. 5:753–759 (1999).

    Google Scholar 

  59. F. Kratz, T. Roth, I. Fichiner, P. Schumacher, H. H. Fiebig, and C. Unger. In vitro and in vivo efficacy of acid-sensitive transferrin and albumin doxorubicin conjugates in a human xenograft panel and in the MDA-MB-435 mamma carcinoma model. J.Drug Target. 8:305–318 (2000).

    Google Scholar 

  60. M. Eatock, N. Church, R. Harris, W. Angerson, C. McArdle, R. French, and C. Twelves. Activity of doxorubicin covalently bound to a novel human serum albumin microcapsule. Invest.New Drugs 17:111–120 (1999).

    Google Scholar 

  61. F. Kratz, J. Drevs, G. Bing, C. Stockmar, K. Scheuermann, P. Lazar, and C. Unger. Development and in vitro efficacy of novel MMP2 and MMP9 specific doxorubicin albumin conjugates. Bioorg.Med.Chem.Lett. 11:2001–2006 (2001).

    Google Scholar 

  62. F. Kratz, U. Beyer, T. Roth, M. T. Schutte, A. Unold, H. H. Fiebig, and C. Unger. Albumin conjugates of the anticancer drug chlorambucil: synthesis, characterization, and in vitro efficacy. Arch.Pharm. 331:47–53 (1998).

    Google Scholar 

  63. G. W. Bos, N. M. Scharenborg, A. A. Poot, G. H. Engbers, T. Beugeling, W. G. van Aken, and J. Feijen. Blood compatibility of surfaces with immobilized albumin-heparin conjugate and effect of endothelial cell seeding on platelet adhesion. J.Biomed.Mater.Res. 47:279–291 (1999).

    Google Scholar 

  64. B. N. Melgert, P. Olinga, V. K. Jack, G. Molema, D. K. Meijer, and K. Poelstra. Dexamethasone coupled to albumin is selectively taken up by rat nonparenchymal liver cells and attenuates LPS-induced activation of hepatic cells. J.Hepatol. 32:603–611 (2000).

    Google Scholar 

  65. C. Albrecht, B. N. Melgert, J. Reichen, K. Poelstra, and D. K. Meijer. Effect of chronic bile duct obstruction and LPS upon targeting of naproxen to the liver using naproxen-albumin conjugate. J.Drug Target. 6:105–117 (1998).

    Google Scholar 

  66. M. E. Kuipers, M. vd Berg, P. J. Swart, J. D Laman, D. K. Meijer, M. H. Koppelman, and H. Huisman. Mechanism of anti-HIV activity of succinylated human serum albumin. Biochem.Pharmacol. 57:889–898 (1999).

    Google Scholar 

  67. C. Cabrera, M. Witvrouw, A. Gutierrez, B. Clotet, M. E. Kuipers, P. J. Swart, D. K. Meijer, J. Desmyter, E. De Clercq, and J. A. Este. Resistance of the human immunodeficiency virus to the inhibitory action of negatively charged albumins on virus binding to CD4. AIDS Res.Hum.Retroviruses. 15:1535–1543 (1999).

    Google Scholar 

  68. P. J. Swart, L. Beljaars, M. E. Kuipers, C. Smit, P. Nieuwenhuis, and D. K. Meijer. Homing of negatively charged albumins to the lymphatic system: general implications for drug targeting to peripheral tissues and viral reservoirs. Biochem.Pharmacol. 58: 1425–1435 (1999).

    Google Scholar 

  69. M. E. Kuipers, P. J. Swart, M. Witvrouw, J. A. Este, D. Reymen, E. De Clercq, and D. K. Meijer. Anti-HIV-1 activity of combinations and covalent conjugates of negatively charged human serum albumins (NCAs) and AZT. J.Drug Target. 6:323–335 (1999).

    Google Scholar 

  70. M. Anraku, K. Yamasaki, T. Maruyama, U. Kragh-Hansen, and M. Otagiri. Effect of oxidative stress on the structure and function of human serum albumin. Pharm.Res. 18:632–639 (2001).

    Google Scholar 

  71. P. Yeh, D. Landais, M. Lemaitre, I. Maury, J. Y. Crenne, J. Becquart, A. Murry-Brelier, F. Boucher, G. Montay, R. Fleer, P. H. Hirel, J. F. Mayaux, and D. Klatzmann. Design of yeastsecreted albumin derivatives for human therapy: biologic and antiviral properties of a serum albumin-CD4 genetic conjugate. Proc.Natl.Acad.Sci.USA 89:1904–1908 (1992).

    Google Scholar 

  72. E. Shinya, X. Dervillez, F. Edwards-Levy, V. Duret, E. Brisson, L. Ylisastigui, M. C. Levy, J. H. Cohen, and D. Klatzmann. In vivo delivery of therapeutic proteins by genetically-modified cells: comparison of organoids and human serum albumin alginate-coated beads. Biomed.Pharmacother. 53:471–483 (1999).

    Google Scholar 

  73. S. Syed, P. D. Schuyler, M. Kulczycky, and W. P. Sheffield. Potent antithrombin activity and delayed clearance from the circulation characterize recombinant hirudin genetically fused to albumin. Blood 89:3243–3252 (1997).

    Google Scholar 

  74. U. Bickel, T. Yoshikawa, and W. M. Pardridge. Delivery of peptides peptides and proteins through the blood-brain barrier. Adv.Drug Deliv.Rev. 46:247–279 (2001).

    Google Scholar 

  75. W. M. Pardridge, D. Triguero, and J. L. Buciak. Beta-endorphin chimeric peptides: transport through the blood-brain barrier in vivo and cleavage of disulfide linkage by brain. Endocrinology 126:977–984 (1990).

    Google Scholar 

  76. S. U. Shin, P. Friden, M. Moran, T. Olson, Y. S. Kang, W. M. Pardridge, and S. L. Morrison. Transferrin-antibody fusion proteins are effective in brain targeting. Proc.Natl.Acad.Sci.USA 92:2820–2824 (1995).

    Google Scholar 

  77. M. L. Penichet, Y. S. Kang, W. M. Pardridge, S. L. Morrison, and S. U. Shin. An antibody-avidin fusion protein specific for the transferrin receptor serves as a delivery vehicle for effective brain targeting: initial applications in anti-HIV antisense drug delivery to the brain. J.Immunol. 163:4421–4426 (1999).

    Google Scholar 

  78. D. M. Skyba, R. J. Price, A. Z. Linka, T. C. Skalak, and S. Kaul. Direct in vivo visualization of intravascular destruction of microbubbles by ultrasound and its local effects on tissue. Circulation 98:290–293 (1998).

    Google Scholar 

  79. R. V. Shohet, S. Chen, Y. T. Zhou, Z. Wang, R. S. Meidell, R. H. Unger, and P. A. Grayburn. Echocardiographic destruction of albumin microbubbles directs gene delivery to the myocardium. Circulation 101:2554–2556 (2000).

    Google Scholar 

  80. E. C. Unger, E. Hersh, M. Vannan, and T. McCreery. Gene delivery using ultrasound contrast agents. Echocardiography 18: 355–361 (2001).

    Google Scholar 

  81. S. Simoes, V. Slepushkin, P. Pires, R. Gaspar, M. C. Pedroso de Lima, and N. Duzgunes. Human serum albumin enhances DNA transfection by lipoplexes and confers resistance to inhibition by serum. Biochim.Biophys.Acta 1463:459–469 (2000).

    Google Scholar 

  82. D. Fischer, T. Bieber, S. Brusselbach, H. Elsasser, and T. Kissel. Cationized human serum albumin as a non-viral vector system for gene delivery? Characterization of complex formation with plasmid DNA and transfection efficiency. Int.J.Pharm. 225:97–111 (2001).

    Google Scholar 

  83. F. M. Orson, B. M. Kinsey, P. J. Hua, B. S. Bhogal, C. L. Densmore, and M. A. Barry. Genetic immunization with lungtargeting macroaggregated polyethyleneimine-albumin conjugates elicits combined systemic and mucosal immune responses. J.Immunol. 164:6313–6321 (2000).

    Google Scholar 

  84. S. Hosono, T. Ohno, H. Kimoto, R. Nagoshi, M. Shimizu, and M. Nozawa. Effects of albumin infusion therapy on total and unbound bilirubin values in term infants with intensive phototherapy. Pediatr.Int. 43:8–11 (2001).

    Google Scholar 

  85. H. Ihara, N. Hashizume, N. Shimizu, and T. Aoki. Threshold concentration of unbound bilirubin to induce neurologic deficits in a patient with type I Crigler-Najjar syndrome. Ann.Clin.Biochem. 36:347–352 (1999).

    Google Scholar 

  86. C. E. Petersen, C. E. Ha, K. Harohalli, J. B. Feix, and N. V. Bhagavan. A dynamic model for bilirubin binding to human serum albumin. J.Biol.Chem. 275:20985–20995 (2000).

    Google Scholar 

  87. C. E. Ha, C. E. Petersen, D. S. Park, K. Harohalli, and N. V. Bhagavan. Identification of key amino acid residues involved in specific interactions between digoxin and human serum albumin. J.Biochem.Mol.Biol.Biophy. 2:201–207 (1999).

    Google Scholar 

  88. T. Abe, T. Abe, S. Ageta, T. Kakuta, N. Suzuki, H. Hirata, M. Shouno, H. Saio, and T. Akizawa. A new method for removal of albumin-binding uremic toxins: efficacy of an albumin-dialysate. Ther.Apher. 5:58–63 (2001).

    Google Scholar 

  89. S. R. Mitzner, J. Stange, S. Klammt, T. Risler, C. M. Erley, B. D. Bader, E. D. Berger, W. Lauchart, P. Peszynski, J. Freytag, H. Hickstein, J. Loock, J. M. Lohr, S. Liebe, J. Emmrich, G. Korten, and R. Schmidt. Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial. Liver Transpl. 6:277–286 (2000).

    Google Scholar 

  90. B. Kreymann, M. Seige, U. Schweigart, K. F. Kopp, and M. Classen. Albumin dialysis: effective removal of copper in a patient with fulminant Wilson disease and successful bridging to liver transplantation: a new possibility for the elimination of proteinbound toxins. J.Hepatol. 31:1080–1085 (1999).

    Google Scholar 

  91. A. Sumi, K. Okuyama, K. Kobayashi, W. Ohtani, T. Ohmura, and K. Yokoyama. Purification of recombinant human serum albumin efficient purification using STREAMLINE. Bioseparation 8:195–200 (1999).

    Google Scholar 

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto, 862-0973, Japan

    Victor Tuan Giam Chuang & Masaki Otagiri

  2. Department of Medical Biochemistry, University of Aarhus, DK-8000, Aarhus C, Denmark

    Ulrich Kragh-Hansen

Authors
  1. Victor Tuan Giam Chuang
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  2. Ulrich Kragh-Hansen
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  3. Masaki Otagiri
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Correspondence to Masaki Otagiri.

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Tuan Giam Chuang, V., Kragh-Hansen, U. & Otagiri, M. Pharmaceutical Strategies Utilizing Recombinant Human Serum Albumin. Pharm Res 19, 569–577 (2002). https://doi.org/10.1023/A:1015396825274

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