Advertisement

Journal of Pharmaceutical Investigation

, Volume 46, Issue 4, pp 305–315 | Cite as

Albumin-based potential drugs: focus on half-life extension and nanoparticle preparation

  • Eun Seong Lee
  • Yu Seok Youn
Review

Abstract

Albumin has been viewed as one of the most useful and versatile carrier proteins in pharmaceutical and clinical fields. Albumin is biocompatible and non-toxic, and so can be used as a pharmaceutical carrier more safely versus many synthetic polymers. Importantly, albumin has great ability to extend circulating half-lives of short-lived peptides and protein drugs when they are properly linked because albumin is hardly filtered in the glomerulus due to its large size (~66.4 kDa). Albumin is also an excellent material to construct nanoparticles because it has good physicochemical stability, targetability, and chemical functionality. In the first part of this review, three major methods for half-life extension of peptide/protein drugs using endogenous or exogenous albumin are described: physical non-covalent binding, covalent binding, and albumin-fusion. The second part details the most intensively utilized methods for nanoparticle preparation: desolvation, nanoparticle albumin bound (Nab™) technology, and self-assembly. The review provides in-depth understanding for albumin-based drugs and their nano-delivery.

Keywords

Albumin Half-life extension Nanoparticles Targeting Cancer Diabetes 

Notes

Acknowledgments

All authors (E. S. Lee and Y. S. Youn) declare that they have no conflict of interest. This article does not contain any studies with human or animal subjects performed by any of the authors. The corresponding author Y. S. Youn would like to express special thanks to the past Dr. Tae Hyung Kim for this review work. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (NRF-2014R1A2A2A05002133).

References

  1. Bae S, Ma K, Kim TH, Lee ES, Oh KT, Park ES, Lee KC, Youn YS (2012) Doxorubicin–loaded human serum albumin nanoparticles surface–modified with TNF–related apoptosis–inducing ligand and transferrin for targeting multiple tumor types. Biomaterials 33(5):1536–1546CrossRefPubMedGoogle Scholar
  2. Baggio LL, Huang Q, Cao X, Drucker DJ (2008) An albumin-exendin-4 conjugate engages central and peripheral circuits regulating murine energy and glucose homeostasis. Gastroenterology 134(4):1137–1147CrossRefPubMedGoogle Scholar
  3. Ballantyne FC, Fleck A, Dick WC (1971) Albumin metabolism in rheumatoid arthritis. Ann Rheum Dis 30(3):265–270CrossRefPubMedPubMedCentralGoogle Scholar
  4. Battogtokh G, Kang JH, Ko YT (2015) Long-circulating self-assembled cholesteryl albumin nanoparticles enhance tumor accumulation of hydrophobic anticancer drug. Eur J Pharm Biopharm 96:96–105CrossRefPubMedGoogle Scholar
  5. Bosse D, Praus M, Kiessling P, Nyman L, Andresen C, Waters J, Schindel F (2005) Phase I comparability of recombinant human albumin and human serum albumin. J Clin Pharmacol 45(1):57–67CrossRefPubMedGoogle Scholar
  6. Byeon HJ, Min SY, Kim I, Lee ES, Oh KT, Shin BS, Lee KC, Youn YS (2014) Human serum albumin-TRAIL conjugate for the treatment of rheumatoid arthritis. Bioconjug Chem 25(12):2212–2221CrossRefPubMedGoogle Scholar
  7. Byeon HJ, le Thao Q, Lee S, Min SY, Lee ES, Shin BS, Choi HG, Youn YS (2016) Doxorubicin-loaded nanoparticles consisted of cationic- and mannose-modified-albumins for dual-targeting in brain tumors. J Control Release 225:301–313CrossRefPubMedGoogle Scholar
  8. Chae SY, Choi YG, Son S, Jung SY, Lee DS, Lee KC (2010) The fatty acid conjugated exendin-4 analogs for type 2 antidiabetic therapeutics. J Control Release 144(1):10–16CrossRefPubMedGoogle Scholar
  9. Chen W, Gu B, Wang H, Pan J, Hou H (2008) Development and evaluation of novel itraconazole-loaded intravenous nanoparticles. Int J Pharm 362(1–2):133–140CrossRefPubMedGoogle Scholar
  10. Choi SH, Byeon HJ, Choi JS, Thao L, Kim I, Lee ES, Shin BS, Lee KC, Youn YS (2015) Inhalable self-assembled albumin nanoparticles for treating drug-resistant lung cancer. J Control Release 197:199–207CrossRefPubMedGoogle Scholar
  11. Chuang VT, Kragh-Hansen U, Otagiri M (2002) Pharmaceutical strategies utilizing recombinant human serum albumin. Pharm Res 19(5):569–577CrossRefPubMedGoogle Scholar
  12. Desai N, Trieu V, Yao Z, Louie L, Ci S, Yang A, Tao C, De T, Beals B, Dykes D, Noker P, Yao R, Labao E, Hawkins M, Soon-Shiong P (2006) Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI–007, compared with cremophor–based paclitaxel. Clin Cancer Res 12(4):1317–1324CrossRefPubMedGoogle Scholar
  13. Dreis S, Rothweiler F, Michaelis M, Cinatl J Jr, Kreuter J, Langer K (2007) Preparation, characterisation and maintenance of drug efficacy of doxorubicin-loaded human serum albumin (HSA) nanoparticles. Int J Pharm 341(1–2):207–214CrossRefPubMedGoogle Scholar
  14. Elsadek B, Kratz F (2012) Impact of albumin on drug delivery—new applications on the horizon. J Control Release 157(1):4–28CrossRefPubMedGoogle Scholar
  15. Gong J, Huo M, Zhou J, Zhang Y, Peng X, Yu D, Zhang H, Li J (2009) Synthesis, characterization, drug-loading capacity and safety of novel octyl modified serum albumin micelles. Int J Pharm 376(1–2):161–168CrossRefPubMedGoogle Scholar
  16. He X, Xiang N, Zhang J, Zhou J, Fu Y, Gong T, Zhang Z (2015) Encapsulation of teniposide into albumin nanoparticles with greatly lowered toxicity and enhanced antitumor activity. Int J Pharm 487(1–2):250–259CrossRefPubMedGoogle Scholar
  17. Hobbs SK, Monsky WL, Yuan F, Roberts WG, Griffith L, Torchilin VP, Jain RK (1998) Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proc Natl Acad Sci USA 95(8):4607–4612CrossRefPubMedPubMedCentralGoogle Scholar
  18. Ibrahim N, Ibrahim H, Dormoi J, Briolant S, Pradines B, Moreno A, Mazier D, Legrand P, Nepveu F (2014) Albumin-bound nanoparticles of practically water–insoluble antimalarial lead greatly enhance its efficacy. Int J Pharm 464(1–2):214–224CrossRefPubMedGoogle Scholar
  19. Ibrahim N, Ibrahim H, Sabater AM, Mazier D, Valentin A, Nepveu F (2015) Artemisinin nanoformulation suitable for intravenous injection: preparation, characterization and antimalarial activities. Int J Pharm 495(2):671–679CrossRefPubMedGoogle Scholar
  20. Juhl CB, Hollingdal M, Sturis J, Jakobsen G, Agersø H, Veldhuis J, Pørksen N, Schmitz O (2002) Bedtime administration of NN2211, a long–acting GLP-1 derivative, substantially reduces fasting and postprandial glycemia in type 2 diabetes. Diabetes 51(2):424–429CrossRefPubMedGoogle Scholar
  21. Kim JG, Baggio LL, Bridon DP, Castaigne JP, Robitaille MF, Jetté L, Benquet C, Drucker DJ (2003) Development and characterization of a glucagon–like peptide 1-albumin conjugate: the ability to activate the glucagon–like peptide 1 receptor in vivo. Diabetes 52(3):751–759CrossRefPubMedGoogle Scholar
  22. Kim I, Kim TH, Ma K, Lee ES, Kim D, Oh KT, Lee DH, Lee KC, Youn YS (2010) Synthesis and evaluation of human serum albumin-modified exendin-4 conjugate via heterobifunctional polyethylene glycol linkage with protracted hypoglycemic efficacy. Bioconjug Chem 21(8):1513–1519CrossRefPubMedGoogle Scholar
  23. Kim H, Park H, Lee J, Kim TH, Lee ES, Oh KT, Lee KC, Youn YS (2011a) Highly porous large poly(lactic-co-glycolic acid) microspheres adsorbed with palmityl-acylated exendin-4 as a long–acting inhalation system for treating diabetes. Biomaterials 32(6):1685–1693CrossRefPubMedGoogle Scholar
  24. Kim TH, Jiang HH, Youn YS, Park CW, Lim SM, Jin CH, Tak KK, Lee HS, Lee KC (2011b) Preparation and characterization of Apo2L/TNF-related apoptosis-inducing ligand-loaded human serum albumin nanoparticles with improved stability and tumor distribution. J Pharm Sci 100(2):482–491CrossRefPubMedGoogle Scholar
  25. Kim TH, Jiang HH, Youn YS, Park CW, Tak KK, Lee S, Kim H, Jon S, Chen X, Lee KC (2011c) Preparation and characterization of water-soluble albumin–bound curcumin nanoparticles with improved antitumor activity. Int J Pharm 403(1–2):285–291CrossRefPubMedGoogle Scholar
  26. Kim I, Choi JS, Lee S, Byeon HJ, Lee ES, Shin BS, Choi HG, Lee KC, Youn YS (2015) In situ facile-forming PEG cross-linked albumin hydrogels loaded with an apoptotic TRAIL protein. J Control Release 214:30–39CrossRefPubMedGoogle Scholar
  27. Kouchakzadeha O, Shojaosadatia SA, Shokrib F (2014) Efficient loading and entrapment of tamoxifen in human serum albumin based nanoparticulate delivery system by a modified desolvation technique. Chem Eng Res Des 92:1681–1692CrossRefGoogle Scholar
  28. Kratz F (2008) Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. J Control Release 132(3):171–183CrossRefPubMedGoogle Scholar
  29. Kurtzhals P, Havelund S, Jonassen I, Markussen J (1997) Effect of fatty acids and selected drugs on the albumin binding of a long-acting, acylated insulin analogue. J Pharm Sci 86(12):1365–1368CrossRefPubMedGoogle Scholar
  30. Langer K, Balthasar S, Vogel V, Dinauer N, von Briesen H, Schubert D (2003) Optimization of the preparation process for human serum albumin (HSA) nanoparticles. Int J Pharm 257(1–2):169–180CrossRefPubMedGoogle Scholar
  31. le Thao Q, Byeon HJ, Lee C, Lee S, Lee ES, Choi HG, Park ES, Youn YS (2016a) Pharmaceutical potential of tacrolimus–loaded albumin nanoparticles having targetability to rheumatoid arthritis tissues. Int J Pharm 497(1–2):268–276CrossRefGoogle Scholar
  32. le Thao Q, Byeon HJ, Lee C, Lee S, Lee ES, Choi YW, Choi HG, Park ES, Lee KC, Youn YS (2016b) Doxorubicin-bound albumin nanoparticles containing a TRAIL protein for targeted treatment of colon cancer. Pharm Res 33(3):615–626CrossRefGoogle Scholar
  33. Lee J, Lee C, Kim I, Moon HR, Kim TH, Oh KT, Lee ES, Lee KC, Youn YS (2012a) Preparation and evaluation of palmitic acid-conjugated exendin-4 with delayed absorption and prolonged circulation for longer hypoglycemia. Int J Pharm 424(1–2):50–57CrossRefPubMedGoogle Scholar
  34. Lee J, Lee C, Kim TH, Chi SC, Moon HR, Oh KT, Lee ES, Lee KC, Youn YS (2012b) Pulmonary administered palmitic–acid modified exendin-4 peptide prolongs hypoglycemia in type 2 diabetic db/db mice. Regul Pept 177(1–3):68–72CrossRefPubMedGoogle Scholar
  35. Léger R, Thibaudeau K, Robitaille M, Quraishi O, van Wyk P, Bousquet-Gagnon N, Carette J, Castaigne JP, Bridon DP (2004) Identification of CJC-1131-albumin bioconjugate as a stable and bioactive GLP-1(7-36) analog. Bioorg Med Chem Lett 14(17):4395–4398CrossRefPubMedGoogle Scholar
  36. Levick JR (1981) Permeability of rheumatoid and normal human synovium to specific plasma proteins. Arthritis Rheum 24(12):1550–1560CrossRefPubMedGoogle Scholar
  37. Li C, Li Y, Gao Y, Wei N, Zhao X, Wang C, Li Y, Xiu X, Cui J (2014) Direct comparison of two albumin–based paclitaxel–loaded nanoparticle formulations: is the crosslinked version more advantageous? Int J Pharm 468(1–2):15–25CrossRefPubMedGoogle Scholar
  38. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65(1–2):271–284CrossRefPubMedGoogle Scholar
  39. Markussen J, Havelund S, Kurtzhals P, Andersen AS, Halstrøm J, Hasselager E, Larsen UD, Ribel U, Schäffer L, Vad K, Jonassen I (1996) Soluble, fatty acid acylated insulins bind to albumin and show protracted action in pigs. Diabetologia 39(3):281–288CrossRefPubMedGoogle Scholar
  40. Mendez CM, McClain CJ, Marsano LS (2005) Albumin therapy in clinical practice. Nutr Clin Pract 20(3):314–320CrossRefPubMedGoogle Scholar
  41. Michaelis K, Hoffmann MM, Dreis S, Herbert E, Alyautdin RN, Michaelis M, Kreuter J, Langer K (2006) Covalent linkage of apolipoprotein e to albumin nanoparticles strongly enhances drug transport into the brain. J Pharmacol Exp Ther 317(3):1246–1253CrossRefPubMedGoogle Scholar
  42. Min SY, Byeon HJ, Lee C, Seo J, Lee ES, Shin BS, Choi HG, Lee KC, Youn YS (2015) Facile one-pot formulation of TRAIL-embedded paclitaxel-bound albumin nanoparticles for the treatment of pancreatic cancer. Int J Pharm 494(1):506–515CrossRefPubMedGoogle Scholar
  43. Moreno-Aspitia A, Perez EA (2005) Nanoparticle albumin-bound paclitaxel (ABI-007): a newer taxane alternative in breast cancer. Future Oncol 1(6):755–762CrossRefPubMedGoogle Scholar
  44. Podhajcer OL, Benedetti LG, Girotti MR, Prada F, Salvatierra E, Llera AS (2008) The role of the matricellular protein SPARC in the dynamic interaction between the tumor and the host. Cancer Metastasis Rev 27(4):691–705CrossRefPubMedGoogle Scholar
  45. Sage H, Johnson C, Bornstein P (1984) Characterization of a novel serum albumin-binding glycoprotein secreted by endothelial cells in culture. J Biol Chem 259(6):3993–4007PubMedGoogle Scholar
  46. Seo J, Lee C, Hwang HS, Kim B, le Thao Q, Lee ES, Oh KT, Lim JL, Choi HG, Youn YS (2016) Therapeutic advantage of inhaled tacrolimus-bound albumin nanoparticles in a bleomycin-induced pulmonary fibrosis mouse model. Pulm Pharmacol Ther 36:53–61CrossRefPubMedGoogle Scholar
  47. Singh KV, Kaur J, Varshney GC, Raje M, Suri CR (2004) Synthesis and characterization of hapten-protein conjugates for antibody production against small molecules. Bioconjug Chem 15(1):168–173CrossRefPubMedGoogle Scholar
  48. Sleep D (2015) Albumin and its application in drug delivery. Expert Opin Drug Deliv 12(5):793–812CrossRefPubMedGoogle Scholar
  49. Son S, Song S, Lee SJ, Min S, Kim SA, Yhee JY, Huh MS, Chan Kwon I, Jeong SY, Byun Y, Kim SH, Kim K (2013) Self-crosslinked human serum albumin nanocarriers for systemic delivery of polymerized siRNA to tumors. Biomaterials 34(37):9475–9485CrossRefPubMedGoogle Scholar
  50. Subramanian GM, Fiscella M, Lamousé-Smith A, Zeuzem S, McHutchison JG (2007) Albinterferon alpha-2b: a genetic fusion protein for the treatment of chronic hepatitis C. Nat Biotechnol 25(12):1411–1419CrossRefPubMedGoogle Scholar
  51. Wagner S, Rothweiler F, Anhorn MG, Sauer D, Riemann I, Weiss EC, Katsen-Globa A, Michaelis M, Cinatl J Jr, Schwartz D, Kreuter J, von Briesen H, Langer K (2010) Enhanced drug targeting by attachment of an anti alphav integrin antibody to doxorubicin loaded human serum albumin nanoparticles. Biomaterials 31(8):2388–2398CrossRefPubMedGoogle Scholar
  52. Weber C, Coester C, Kreuter J, Langer K (2000) Desolvation process and surface characterisation of protein nanoparticles. Int J Pharm 194(1):91–102CrossRefPubMedGoogle Scholar
  53. Wilkinson P, Jeremy R, Brooks FP, Hollander JL (1965) The mechanism of hypoalbuminemia in rheumatoid arthritis. Ann Intern Med 63:109–114CrossRefPubMedGoogle Scholar
  54. Wilson B, Lavanya Y, Priyadarshini SR, Ramasamy M, Jenita JL (2014) Albumin nanoparticles for the delivery of gabapentin: preparation, characterization and pharmacodynamic studies. Int J Pharm 473(1–2):73–79CrossRefPubMedGoogle Scholar
  55. Xu R, Fisher M, Juliano RL (2011) Targeted albumin-based nanoparticles for delivery of amphipathic drugs. Bioconjug Chem. 22(5):870–878CrossRefPubMedPubMedCentralGoogle Scholar
  56. Yang Z, Gong W, Wang Z, Li B, Li M, Xie X, Zhang H, Yang Y, Li Z, Li Y, Yu F, Mei X (2015) A novel drug-polyethylene glycol liquid compound method to prepare 10-hydroxycamptothecin loaded human serum albumin nanoparticle. Int J Pharm 490(1–2):412–428CrossRefPubMedGoogle Scholar
  57. Yuan A, Wu J, Song C, Tang X, Qiao Q, Zhao L, Gong G, Hu Y (2013) A novel self-assembly albumin nanocarrier for reducing doxorubicin-mediated cardiotoxicity. J Pharm Sci 102(5):1626–1635CrossRefPubMedGoogle Scholar
  58. Zhang S, Kucharski C, Doschak MR, Sebald W, Uludağ H (2010) Polyethylenimine-PEG coated albumin nanoparticles for BMP-2 delivery. Biomaterials 31(5):952–963CrossRefPubMedGoogle Scholar
  59. Zhao L, Zhou Y, Gao Y, Ma S, Zhang C, Li J, Wang D, Li X, Li C, Liu Y, Li X (2015) Bovine serum albumin nanoparticles for delivery of tacrolimus to reduce its kidney uptake and functional nephrotoxicity. Int J Pharm 483(1–2):180–187CrossRefPubMedGoogle Scholar
  60. Zimmera AK, Zerbe H, Kreuter J (1994) Evaluation of pilocarpine-loaded albumin particles as drug delivery systems for controlled delivery in the eye I. In vitro and in vivo characterization. J Control Release 32(1):57–70CrossRefGoogle Scholar

Copyright information

© The Korean Society of Pharmaceutical Sciences and Technology 2016

Authors and Affiliations

  1. 1.Division of BiotechnologyThe Catholic University of KoreaBucheon-siRepublic of Korea
  2. 2.School of PharmacySungkyunkwan UniversitySuwonRepublic of Korea

Personalised recommendations