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

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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.

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References

  • 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):1536–1546

    Article  CAS  PubMed  Google Scholar 

  • 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):1137–1147

    Article  CAS  PubMed  Google Scholar 

  • Ballantyne FC, Fleck A, Dick WC (1971) Albumin metabolism in rheumatoid arthritis. Ann Rheum Dis 30(3):265–270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 96:96–105

    Article  CAS  PubMed  Google Scholar 

  • 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):57–67

    Article  CAS  PubMed  Google Scholar 

  • 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):2212–2221

    Article  CAS  PubMed  Google Scholar 

  • 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 225:301–313

    Article  CAS  PubMed  Google Scholar 

  • 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):10–16

    Article  CAS  PubMed  Google Scholar 

  • 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):133–140

    Article  CAS  PubMed  Google Scholar 

  • 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 197:199–207

    Article  CAS  PubMed  Google Scholar 

  • Chuang VT, Kragh-Hansen U, Otagiri M (2002) Pharmaceutical strategies utilizing recombinant human serum albumin. Pharm Res 19(5):569–577

    Article  PubMed  Google Scholar 

  • 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):1317–1324

    Article  CAS  PubMed  Google Scholar 

  • 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):207–214

    Article  CAS  PubMed  Google Scholar 

  • Elsadek B, Kratz F (2012) Impact of albumin on drug delivery—new applications on the horizon. J Control Release 157(1):4–28

    Article  CAS  PubMed  Google Scholar 

  • 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):161–168

    Article  CAS  PubMed  Google Scholar 

  • 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):250–259

    Article  CAS  PubMed  Google Scholar 

  • 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):4607–4612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):214–224

    Article  CAS  PubMed  Google Scholar 

  • 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):671–679

    Article  CAS  PubMed  Google Scholar 

  • 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):424–429

    Article  CAS  PubMed  Google Scholar 

  • 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):751–759

    Article  CAS  PubMed  Google Scholar 

  • 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):1513–1519

    Article  CAS  PubMed  Google Scholar 

  • 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):1685–1693

    Article  CAS  PubMed  Google Scholar 

  • 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):482–491

    Article  CAS  PubMed  Google Scholar 

  • 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):285–291

    Article  CAS  PubMed  Google Scholar 

  • 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 214:30–39

    Article  CAS  PubMed  Google Scholar 

  • 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 92:1681–1692

    Article  Google Scholar 

  • Kratz F (2008) Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. J Control Release 132(3):171–183

    Article  CAS  PubMed  Google Scholar 

  • 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):1365–1368

    Article  CAS  PubMed  Google Scholar 

  • 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):169–180

    Article  CAS  PubMed  Google Scholar 

  • 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):268–276

    Article  CAS  Google Scholar 

  • 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):615–626

    Article  CAS  Google Scholar 

  • 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):50–57

    Article  CAS  PubMed  Google Scholar 

  • 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):68–72

    Article  CAS  PubMed  Google Scholar 

  • 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):4395–4398

    Article  PubMed  Google Scholar 

  • Levick JR (1981) Permeability of rheumatoid and normal human synovium to specific plasma proteins. Arthritis Rheum 24(12):1550–1560

    Article  CAS  PubMed  Google Scholar 

  • 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):15–25

    Article  CAS  PubMed  Google Scholar 

  • 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):271–284

    Article  CAS  PubMed  Google Scholar 

  • 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):281–288

    Article  CAS  PubMed  Google Scholar 

  • Mendez CM, McClain CJ, Marsano LS (2005) Albumin therapy in clinical practice. Nutr Clin Pract 20(3):314–320

    Article  PubMed  Google Scholar 

  • 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):1246–1253

    Article  CAS  PubMed  Google Scholar 

  • 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):506–515

    Article  CAS  PubMed  Google Scholar 

  • Moreno-Aspitia A, Perez EA (2005) Nanoparticle albumin-bound paclitaxel (ABI-007): a newer taxane alternative in breast cancer. Future Oncol 1(6):755–762

    Article  CAS  PubMed  Google Scholar 

  • 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):691–705

    Article  CAS  PubMed  Google Scholar 

  • 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):3993–4007

    CAS  PubMed  Google Scholar 

  • 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 36:53–61

    Article  CAS  PubMed  Google Scholar 

  • 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):168–173

    Article  CAS  PubMed  Google Scholar 

  • Sleep D (2015) Albumin and its application in drug delivery. Expert Opin Drug Deliv 12(5):793–812

    Article  CAS  PubMed  Google Scholar 

  • 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):9475–9485

    Article  CAS  PubMed  Google Scholar 

  • 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):1411–1419

    Article  CAS  PubMed  Google Scholar 

  • 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):2388–2398

    Article  CAS  PubMed  Google Scholar 

  • Weber C, Coester C, Kreuter J, Langer K (2000) Desolvation process and surface characterisation of protein nanoparticles. Int J Pharm 194(1):91–102

    Article  CAS  PubMed  Google Scholar 

  • Wilkinson P, Jeremy R, Brooks FP, Hollander JL (1965) The mechanism of hypoalbuminemia in rheumatoid arthritis. Ann Intern Med 63:109–114

    Article  CAS  PubMed  Google Scholar 

  • 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):73–79

    Article  CAS  PubMed  Google Scholar 

  • Xu R, Fisher M, Juliano RL (2011) Targeted albumin-based nanoparticles for delivery of amphipathic drugs. Bioconjug Chem. 22(5):870–878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):412–428

    Article  CAS  PubMed  Google Scholar 

  • 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):1626–1635

    Article  CAS  PubMed  Google Scholar 

  • Zhang S, Kucharski C, Doschak MR, Sebald W, Uludağ H (2010) Polyethylenimine-PEG coated albumin nanoparticles for BMP-2 delivery. Biomaterials 31(5):952–963

    Article  PubMed  Google Scholar 

  • 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):180–187

    Article  CAS  PubMed  Google Scholar 

  • 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):57–70

    Article  Google Scholar 

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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).

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  1. Division of Biotechnology, The Catholic University of Korea, 43-1 Yeokgok 2-dong, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea

    Eun Seong Lee

  2. School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea

    Yu Seok Youn

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Correspondence to Yu Seok Youn.

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Lee, E.S., Youn, Y.S. Albumin-based potential drugs: focus on half-life extension and nanoparticle preparation. Journal of Pharmaceutical Investigation 46, 305–315 (2016). https://doi.org/10.1007/s40005-016-0250-3

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