Albumin-based drug delivery: harnessing nature to cure disease

  • Maja Larsen
  • Matthias Kuhlmann
  • Michael Hvam
  • Kenneth Howard
Keywords: human serum albumin (HSA), Drugs, Albumin-binding, Albumin fusions, Half-life extension, intracellular delivery, Neonatal Fc receptor (FcRn), Molecular medicine, Targeted drug delivery

Abstract

Abstract
The effectiveness of a drug is dependent on accumulation at the site of action at therapeutic levels, however,
challenges such as rapid renal clearance, degradation or non-specific accumulation requires drug delivery
enabling technologies. Albumin is a natural transport protein with multiple ligand binding sites, cellular
receptor engagement, and a long circulatory half-life due to interaction with the recycling neonatal Fc
receptor. Exploitation of these properties promotes albumin as an attractive candidate for half-life extension
and targeted intracellular delivery of drugs attached by covalent conjugation, genetic fusions, association or
ligand-mediated association. This review will give an overview of albumin-based products with focus on the
natural biological properties and molecular interactions that can be harnessed for the design of a next-generation drug
delivery platform.

Downloads

Download data is not yet available.

References

References

Markovsky E, Baabur-Cohen H, Eldar-Boock A, Omer L, Tiram G, Ferber S, et al.

Administration, distribution, metabolism and elimination of polymer therapeutics.

J Control Release. 2012;161(2):446–60. doi:10.1016/j.jconrel.2011.12.021.

Sleep D, Cameron J, Evans LR. Albumin as a versatile platform for

drug half-life extension. Biochim Biophys Acta. 2013;1830(12):5526–34.

doi:10.1016/j.bbagen.2013.04.023.

Abuchowski A, McCoy JR, Palczuk NC, van Es T, Davis FF. Effect of covalent

attachment of polyethylene glycol on immunogenicity and circulating life

of bovine liver catalase. J Biol Chem. 1977;252(11):3582–6.

Rajender Reddy K, Modi MW, Pedder S. Use of peginterferon alfa-2a (40 KD)

(Pegasys) for the treatment of hepatitis C. Adv Drug Deliv Rev. 2002;54(4):571–86.

Pasut G, Veronese FM. Polymer–drug conjugation, recent achievements

and general strategies. Prog Polym Sci. 2007;32(8–9):933–61.

doi:10.1016/j.progpolymsci.2007.05.008.

Howard KA, Dong M, Oupicky D, Bisht HS, Buss C, Besenbacher F,

et al. Nanocarrier stimuli-activated gene delivery. Small. 2007;3(1):54–7.

doi:10.1002/smll.200600328.

Wilczewska AZ, Niemirowicz K, Markiewicz KH, Car H. Nanoparticles as drug

delivery systems. Pharmacol Rep. 2012;64(5):1020–37.

Howard KA. Delivery of RNA interference therapeutics using polycation-based

nanoparticles. Advanced drug delivery reviews. 2009;61(9):710-20. doi:10.1016/j.

addr.2009.04.001.

Peer D. Harnessing RNAi nanomedicine for precision therapy. Mol Cell Ther.

;2:5. doi:10.1186/2052-8426-2-5.

Peters T. All about albumin: biochemistry, genetics, and medical

applications. San Diego, Calif: Academic; 1996.

Kratz F. Albumin as a drug carrier: Design of prodrugs, drug

conjugates and nanoparticles. J Control Release. 2008;132(3):171–83.

http://dx.doi.org/10.1016/j.jconrel.2008.05.010.

Garcovich M, Zocco MA, Gasbarrini A. Clinical use of albumin in hepatology.

Blood Transfus. 2009;7(4):268–77. doi:10.2450/2008.0080-08.

Anderson CL, Chaudhury C, Kim J, Bronson CL, Wani MA, Mohanty S.

Perspective – FcRn transports albumin: relevance to immunology and

medicine. Trends Immunol. 2006;27(7):343–8. doi:10.1016/j.it.2006.05.004.

Kim J, Hayton WL, Robinson JM, Anderson CL. Kinetics of FcRn-mediated

recycling of IgG and albumin in human: Pathophysiology and therapeutic

implications using a simplified mechanism-based model. Clin Immunol.

;122(2):146–55. doi:10.1016/j.clim.2006.09.001.

Morris MA, Preddy L. Glycosylation accelerates albumin degradation in

normal and diabetic dogs. Biochem Med Metab Biol. 1986;35(3):267–70.

Williams SK, Devenny JJ, Bitensky MW. Micropinocytic ingestion of

glycosylated albumin by isolated microvessels: possible role in pathogenesis

of diabetic microangiopathy. Proc Natl Acad Sci U S A. 1981;78(4):2393–7.

Quinlan GJ, Martin GS, Evans TW. Albumin: biochemical properties and

therapeutic potential. Hepatology. 2005;41(6):1211–9. doi:10.1002/hep.20720.

Sudlow G, Birkett DJ, Wade DN. The characterization of two specific drug

binding sites on human serum albumin. Mol Pharmacol. 1975;11(6):824–32.

Kragh-Hansen U, Chuang VT, Otagiri M. Practical aspects of the ligandbinding

and enzymatic properties of human serum albumin. Biol Pharm

Bull. 2002;25(6):695–704.

Petitpas I, Bhattacharya AA, Twine S, East M, Curry S. Crystal structure

analysis of warfarin binding to human serum albumin: anatomy of drug

site I. J Biol Chem. 2001;276(25):22804–9. doi:10.1074/jbc.M100575200.

Sjoholm I, Ekman B, Kober A, Ljungstedt-Pahlman I, Seiving B, Sjodin T.

Binding of drugs to human serum albumin:XI. The specificity of three

binding sites as studied with albumin immobilized in microparticles. Mol

Pharmacol. 1979;16(3):767–77.

Bhattacharya AA, Curry S, Franks NP. Binding of the general anesthetics

propofol and halothane to human serum albumin. High resolution crystal

structures. J Biol Chem. 2000;275(49):38731–8. doi:10.1074/jbc.M005460200.

Benet LZ, Spahn-Langguth H, Iwakawa S, Volland C, Mizuma T, Mayer S,

et al. Predictability of the covalent binding of acidic drugs in man. Life Sci.

;53(8):L141–6.

Williams AM, Dickinson RG. Studies on the reactivity of acyl glucuronides–VI.

Modulation of reversible and covalent interaction of diflunisal acyl

glucuronide and its isomers with human plasma protein in vitro. Biochem

Pharmacol. 1994;47(3):457–67.

Bertucci C, Domenici E. Reversible and covalent binding of drugs to human

serum albumin: methodological approaches and physiological relevance.

Curr Med Chem. 2002;9(15):1463–81.

Kratz F, Abu Ajaj K, Warnecke A. Anticancer carrier-linked prodrugs

in clinical trials. Expert Opin Investig Drugs. 2007;16(7):1037–58.

doi:10.1517/13543784.16.7.1037.

Schnitzer JE, Oh P. Antibodies to SPARC inhibit albumin binding

to SPARC, gp60, and microvascular endothelium. Am J Physiol.

;263(6 Pt 2):H1872–9.

Chaudhury C, Mehnaz S, Robinson JM, Hayton WL, Pearl DK, Roopenian DC,

et al. The major histocompatibility complex-related Fc receptor for IgG (FcRn)

binds albumin and prolongs its lifespan. J Exp Med. 2003;197(3):315–22.

Birn H, Fyfe JC, Jacobsen C, Mounier F, Verroust PJ, Orskov H, et al. Cubilin is

an albumin binding protein important for renal tubular albumin

reabsorption. J Clin Investig. 2000;105(10):1353–61. doi:10.1172/JCI8862.

Cui S, Verroust PJ, Moestrup SK, Christensen EI. Megalin/gp330 mediates uptake

of albumin in renal proximal tubule. Am J Physiol. 1996;271(4 Pt 2):F900–7.

Schnitzer JE, Sung A, Horvat R, Bravo J. Preferential interaction of albuminbinding

proteins, gp30 and gp18, with conformationally modified albumins.

Presence in many cells and tissues with a possible role in catabolism. J Biol

Chem. 1992;267(34):24544–53.

Ghinea N, Fixman A, Alexandru D, Popov D, Hasu M, Ghitescu L, et al.

Identification of albumin-binding proteins in capillary endothelial cells. J Cell

Biol. 1988;107(1):231–9.

Sage H, Johnson C, Bornstein P. Characterization of a novel serum albuminbinding

glycoprotein secreted by endothelial cells in culture. J Biol Chem.

;259(6):3993–4007.

Ghinea N, Eskenasy M, Simionescu M, Simionescu N. Endothelial albumin

binding proteins are membrane-associated components exposed on the

cell surface. J Biol Chem. 1989;264(9):4755–8.

Schnitzer JE, Carley WW, Palade GE. Albumin interacts specifically with a

-kDa microvascular endothelial glycoprotein. Proc Natl Acad Sci U S A.

;85(18):6773–7.

Schnitzer JE, Oh P. Albondin-mediated capillary permeability to albumin.

Differential role of receptors in endothelial transcytosis and endocytosis of

native and modified albumins. J Biol Chem. 1994;269(8):6072–82.

Tiruppathi C, Finnegan A, Malik AB. Isolation and characterization of a cell

surface albumin-binding protein from vascular endothelial cells. Proc Natl

Acad Sci U S A. 1996;93(1):250–4.

Schnitzer JE. gp60 is an albumin-binding glycoprotein expressed by

continuous endothelium involved in albumin transcytosis. Am J Physiol.

;262(1 Pt 2):H246–54.

Iancu C, Mocan L, Bele C, Orza AI, Tabaran FA, Catoi C, et al.

Enhanced laser thermal ablation for the in vitro treatment of liver

cancer by specific delivery of multiwalled carbon nanotubes

functionalized with human serum albumin. Int J Nanomedicine.

;6:129–41. doi:10.2147/IJN.S15841.

Larsen et al. Molecular and Cellular Therapies (2016) 4:3 Page 9 of 12

Schnitzer JE. Update on the cellular and molecular basis of capillary permeability.

Trends Cardiovasc Med. 1993;3(4):124–30. doi:10.1016/1050-1738(93)90012-U.

Schnitzer JE, Allard J, Oh P. NEM inhibits transcytosis, endocytosis, and

capillary permeability: implication of caveolae fusion in endothelia. Am J

Physiol. 1995;268(1 Pt 2):H48–55.

Schnitzer JE, Bravo J. High affinity binding, endocytosis, and degradation of

conformationally modified albumins. Potential role of gp30 and gp18 as

novel scavenger receptors. J Biol Chem. 1993;268(10):7562–70.

Tiruppathi C, Song W, Bergenfeldt M, Sass P, Malik AB. Gp60 activation

mediates albumin transcytosis in endothelial cells by tyrosine kinasedependent

pathway. J Biol Chem. 1997;272(41):25968–75.

Ghitescu L, Fixman A, Simionescu M, Simionescu N. Specific binding sites for

albumin restricted to plasmalemmal vesicles of continuous capillary

endothelium: receptor-mediated transcytosis. J Cell Biol. 1986;102(4):1304–11.

Merlot AM, Kalinowski DS, Richardson DR. Unraveling the mysteries of

serum albumin-more than just a serum protein. Front Physiol. 2014;5:299.

doi:10.3389/fphys.2014.00299.

Schnitzer J, Oh P. Antibodies to the albumin binding protein, albondin, inhibit

transvascular transport of albumin in the rat lung. FASEB Journal. 1993;7(3–4):A902.

Sage H, Vernon RB, Funk SE, Everitt EA, Angello J. SPARC, a secreted protein

associated with cellular proliferation, inhibits cell spreading in vitro and

exhibits Ca + 2-dependent binding to the extracellular matrix. J Cell Biol.

;109(1):341–56.

Brekken RA, Sage EH. SPARC, a matricellular protein: at the crossroads of

cell-matrix. Matrix Biol. 2000;19(7):569–80.

Jacob K, Webber M, Benayahu D, Kleinman HK. Osteonectin promotes

prostate cancer cell migration and invasion: a possible mechanism for

metastasis to bone. Cancer Res. 1999;59(17):4453–7.

Kato Y, Sakai N, Baba M, Kaneko S, Kondo K, Kubota Y, et al. Stimulation of

motility of human renal cell carcinoma by SPARC/Osteonectin/BM-40

associated with type IV collagen. Invasion Metastasis. 1998;18(2):105–14.

Lane TF, Sage EH. The biology of SPARC, a protein that modulates cellmatrix

interactions. FASEB J. 1994;8(2):163–73.

Pichler RH, Hugo C, Shankland SJ, Reed MJ, Bassuk JA, Andoh TF, et al.

SPARC is expressed in renal interstitial fibrosis and in renal vascular injury.

Kidney Int. 1996;50(6):1978–89.

Pichler RH, Bassuk JA, Hugo C, Reed MJ, Eng E, Gordon KL, et al. SPARC is

expressed by mesangial cells in experimental mesangial proliferative

nephritis and inhibits platelet-derived-growth-factor-medicated mesangial

cell proliferation in vitro. Am J Pathol. 1996;148(4):1153–67.

Desai N, Trieu V, Damascelli B, Soon-Shiong P. SPARC Expression Correlates

with Tumor Response to Albumin-Bound Paclitaxel in Head and Neck

Cancer Patients. Transl Oncol. 2009;2(2):59–64.

Ottnad E, Via DP, Frubis J, Sinn H, Friedrich E, Ziegler R, et al. Differentiation

of binding sites on reconstituted hepatic scavenger receptors using

oxidized low-density lipoprotein. Biochem J. 1992;281(Pt 3):745–51.

Zhang H, Yang Y, Steinbrecher UP. Structural requirements for the binding

of modified proteins to the scavenger receptor of macrophages. J Biol

Chem. 1993;268(8):5535–42.

Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol.

Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J

Med. 1989;320(14):915–24. doi:10.1056/NEJM198904063201407.

Storm T, Emma F, Verroust PJ, Hertz JM, Nielsen R, Christensen EI. A patient with

cubilin deficiency. N Engl J Med. 2011;364(1):89–91. doi:10.1056/NEJMc1009804.

Amsellem S, Gburek J, Hamard G, Nielsen R, Willnow TE, Devuyst O, et al.

Cubilin is essential for albumin reabsorption in the renal proximal tubule.

J Am Soc Nephrol. 2010;21(11):1859–67. doi:10.1681/ASN.2010050492.

Weyer K, Storm T, Shan J, Vainio S, Kozyraki R, Verroust PJ, et al. Mouse

model of proximal tubule endocytic dysfunction. Nephrol Dial Transplant.

;26(11):3446–51. doi:10.1093/ndt/gfr525.

Christensen EI, Birn H, Storm T, Weyer K, Nielsen R. Endocytic

receptors in the renal proximal tubule. Physiology. 2012;27(4):223–36.

doi:10.1152/physiol.00022.2012.

Zhai XY, Nielsen R, Birn H, Drumm K, Mildenberger S, Freudinger R,

et al. Cubilin- and megalin-mediated uptake of albumin in cultured

proximal tubule cells of opossum kidney. Kidney Int. 2000;58(4):1523–33.

doi:10.1046/j.1523-1755.2000.00314.x.

Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age.

Nat Rev Immunol. 2007;7(9):715–25. doi:10.1038/nri2155.

Zhu X, Peng J, Raychowdhury R, Nakajima A, Lencer WI, Blumberg RS. The

heavy chain of neonatal Fc receptor for IgG is sequestered in endoplasmic

reticulum by forming oligomers in the absence of beta2-microglobulin

association. Biochem J. 2002;367(Pt 3):703–14. doi:10.1042/BJ20020200.

Roopenian DC, Christianson GJ, Sproule TJ, Brown AC, Akilesh S,

Jung N, et al. The MHC class I-like IgG receptor controls perinatal

IgG transport, IgG homeostasis, and fate of IgG-Fc-coupled drugs.

J Immunol. 2003;170(7):3528–33.

Junghans RP, Anderson CL. The protection receptor for IgG catabolism is

the beta2-microglobulin-containing neonatal intestinal transport receptor.

Proc Natl Acad Sci U S A. 1996;93(11):5512–6.

Ghetie V, Hubbard JG, Kim JK, Tsen MF, Lee Y, Ward ES. Abnormally short

serum half-lives of IgG in beta 2-microglobulin-deficient mice. Eur J

Immunol. 1996;26(3):690–6. doi:10.1002/eji.1830260327.

Andersen JT, Dalhus B, Cameron J, Daba MB, Plumridge A, Evans L, et al.

Structure-based mutagenesis reveals the albumin-binding site of the

neonatal Fc receptor. Nat Commun. 2012;3:610. doi:10.1038/ncomms1607.

Andersen JT, Daba MB, Sandlie I. FcRn binding properties of an abnormal

truncated analbuminemic albumin variant. Clin Biochem. 2010;43(4–5):367–72.

doi:10.1016/j.clinbiochem.2009.12.001.

Bern M, Sand KM, Nilsen J, Sandlie I, Andersen JT. The role of albumin

receptors in regulation of albumin homeostasis: Implications for drug delivery.

J Control Release. 2015;211:144–62. doi:10.1016/j.jconrel.2015.06.006.

Sand KM, Bern M, Nilsen J, Dalhus B, Gunnarsen KS, Cameron J, et al.

Interaction with both domain I and III of albumin is required for optimal

pH-dependent binding to the neonatal Fc receptor (FcRn). J Biol Chem.

;289(50):34583–94. doi:10.1074/jbc.M114.587675.

Schmidt MM, Townson SA, Andreucci AJ, King BM, Schirmer EB, Murillo AJ,

et al. Crystal structure of an HSA/FcRn complex reveals recycling by

competitive mimicry of HSA ligands at a pH-dependent hydrophobic

interface. Structure. 2013;21(11):1966–78. doi:10.1016/j.str.2013.08.022.

Oganesyan V, Damschroder MM, Cook KE, Li Q, Gao C, Wu H, et al.

Structural insights into neonatal Fc receptor-based recycling mechanisms.

J Biol Chem. 2014;289(11):7812–24. doi:10.1074/jbc.M113.537563.

Chaudhury C, Brooks CL, Carter DC, Robinson JM, Anderson CL. Albumin

binding to FcRn: distinct from the FcRn-IgG interaction. Biochemistry.

;45(15):4983–90. doi:10.1021/bi052628y.

Andersen JT, Dee Qian J, Sandlie I. The conserved histidine 166 residue

of the human neonatal Fc receptor heavy chain is critical for the pHdependent

binding to albumin. Eur J Immunol. 2006;36(11):3044–51.

doi:10.1002/eji.200636556.

West Jr AP, Bjorkman PJ. Crystal structure and immunoglobulin G binding

properties of the human major histocompatibility complex-related Fc

receptor(,). Biochemistry. 2000;39(32):9698–708.

Mezo AR, Sridhar V, Badger J, Sakorafas P, Nienaber V. X-ray crystal

structures of monomeric and dimeric peptide inhibitors in complex with

the human neonatal Fc receptor, FcRn. J Biol Chem. 2010;285(36):27694–701.

doi:10.1074/jbc.M110.120667.

Sand KM, Dalhus B, Christianson GJ, Bern M, Foss S, Cameron J, et al.

Dissection of the neonatal Fc receptor (FcRn)-albumin interface using

mutagenesis and anti-FcRn albumin-blocking antibodies. J Biol Chem.

;289(24):17228–39. doi:10.1074/jbc.M113.522565.

Malkinson M. The transmission of passive immunity to Escherichia coli from

mother to young in the domestic fowl (Gallus domesticus). Immunology.

;9(4):311–7.

Schultze HE, Heremans JF. Molecular biology of human proteins: with

special reference to plasma proteins. Nature and Metabolism of Extracellular

Proteins, vol 1. New York Elsevier 1966.

Andersen JT, Sandlie I. The versatile MHC class I-related FcRn protects IgG and

albumin from degradation: implications for development of new diagnostics

and therapeutics. Drug Metab Pharmacokinet. 2009;24(4):318–32.

Dornhorst A, Luddeke HJ, Sreenan S, Koenen C, Hansen JB, Tsur A, et al.

Safety and efficacy of insulin detemir in clinical practice: 14-week follow-up

data from type 1 and type 2 diabetes patients in the PREDICTIVE European

cohort. Int J Clin Pract. 2007;61(3):523–8. doi:10.1111/j.1742-1241.2007.01316.x.

Marre M, Shaw J, Brandle M, Bebakar WM, Kamaruddin NA, Strand J,

et al. Liraglutide, a once-daily human GLP-1 analogue, added to a

sulphonylurea over 26 weeks produces greater improvements in

glycaemic and weight control compared with adding rosiglitazone or

placebo in subjects with Type 2 diabetes (LEAD-1 SU). Diabet Med.

;26(3):268–78. doi:10.1111/j.1464-5491.2009.02666.x.

Nauck M, Frid A, Hermansen K, Shah NS, Tankova T, Mitha IH, et al. Efficacy

and safety comparison of liraglutide, glimepiride, an

combination with metformin, in type 2 diabetes: the LEAD (liraglutide

effect and action in diabetes)-2 study. Diabetes Care. 2009;32(1):84–90.

doi:10.2337/dc08-1355.

Zinman B, Gerich J, Buse JB, Lewin A, Schwartz S, Raskin P, et al. Efficacy

and safety of the human glucagon-like peptide-1 analog liraglutide in

combination with metformin and thiazolidinedione in patients with

type 2 diabetes (LEAD-4 Met + TZD). Diabetes Care. 2009;32(7):1224–30.

doi:10.2337/dc08-2124.

Russell-Jones D, Vaag A, Schmitz O, Sethi BK, Lalic N, Antic S, et al.

Liraglutide vs insulin glargine and placebo in combination with metformin

and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met + SU):

a randomised controlled trial. Diabetologia. 2009;52(10):2046–55.

doi:10.1007/s00125-009-1472-y.

Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, et al.

Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a

-week randomised, parallel-group, multinational, open-label trial (LEAD-6).

Lancet. 2009;374(9683):39–47. doi:10.1016/S0140-6736(09)60659-0.

Pratley RE, Nauck M, Bailey T, Montanya E, Cuddihy R, Filetti S, et al.

Liraglutide versus sitagliptin for patients with type 2 diabetes who did

not have adequate glycaemic control with metformin: a 26-week,

randomised, parallel-group, open-label trial. Lancet. 2010;375(9724):1447–56.

doi:10.1016/S0140-6736(10)60307-8.

Buse JB, Sesti G, Schmidt WE, Montanya E, Chang CT, Xu Y, et al. Switching

to once-daily liraglutide from twice-daily exenatide further improves

glycemic control in patients with type 2 diabetes using oral agents.

Diabetes Care. 2010;33(6):1300–3. doi:10.2337/dc09-2260.

Ablynx. http://www.ablynx.com/rd-portfolio/clinical-programmes/ozoralizumab/.

Accessed 13 Nov 2015.

Ablynx. http://hugin.info/137912/R/1516627/452958.pdf. Accessed Nov 13

Desai N, Trieu V, Yao Z, Louie L, Ci S, Yang A, et al. 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. 2006;12(4):1317–24.

doi:10.1158/1078-0432.CCR-05-1634.

Neesse A, Frese KK, Chan DS, Bapiro TE, Howat WJ, Richards FM, et al. SPARC

independent drug delivery and antitumour effects of nab-paclitaxel in genetically

engineered mice. Gut. 2014;63(6):974–83. doi:10.1136/gutjnl-2013-305559.

Desai N. Nab technology: a drug delivery platform utilizing endothelial

gp60 receptor-based transport and tumour-derived SPARC for targeting.

Drug Delivery report. 2007; 37–41.

Clinical Trials NCT00477529. https://www.clinicaltrials.gov/ct2/ct2/show/

NCT00477529. 916 Accessed Nov 13 2015.

Clinical Trials NCT02009332. https://www.clinicaltrials.gov/ct2/ct2/show/

NCT02009332. 918 Accessed Nov 13 2015.

Clinical Trials NCT00820768. https://www.clinicaltrials.gov/ct2/ct2/show/

NCT00820768?920term=ABI-010&rank=1. Accessed Nov 13 2015.

Rink T, Heuser T, Fitz H, Schroth HJ, Weller E, Zippel HH.

Lymphoscintigraphic sentinel node imaging and gamma probe detection

in breast cancer with Tc-99 m nanocolloidal albumin: results of an

optimized protocol. Clin Nucl Med. 2001;26(4):293–8.

Wang YF, Chuang MH, Chiu JS, Cham TM, Chung MI. On-site preparation of

technetium-99 m labeled human serum albumin for clinical application.

Tohoku J Exp Med. 2007;211(4):379–85.

Adams BK, Al Attia HM, Khadim RA, Al Haider ZY. 99Tc(m) nanocolloid

scintigraphy: a reliable way to detect active joint disease in patients with

peripheral joint pain. Nucl Med Commun. 2001;22(3):315–8.

Liberatore M, Clemente M, Iurilli AP, Zorzin L, Marini M, Di Rocco E,

et al. Scintigraphic evaluation of disease activity in rheumatoid

arthritis: a comparison of technetium-99 m human non-specific

immunoglobulins, leucocytes and albumin nanocolloids. Eur J Nucl

Med. 1992;19(10):853–7.

Rosenstock J, Reusch J, Bush M, Yang F, Stewart M, Albiglutide SG. Potential

of albiglutide, a long-acting GLP-1 receptor agonist, in type 2 diabetes:

a randomized controlled trial exploring weekly, biweekly, and monthly

dosing. Diabetes Care. 2009;32(10):1880–6. doi:10.2337/dc09-0366.

Bush MA, Matthews JE, De Boever EH, Dobbins RL, Hodge RJ, Walker SE,

et al. Safety, tolerability, pharmacodynamics and pharmacokinetics of

albiglutide, a long-acting glucagon-like peptide-1 mimetic, in healthy

subjects. Diabetes Obes Metab. 2009;11(5):498–505. doi:10.1111/j.1463-

2008.00992.x.

Woodward HN, Anderson SL. Once-weekly albiglutide in the

management of type 2 diabetes: patient considerations. Patient Prefer

Adherence. 2014;8:789–803. doi:10.2147/PPA.S53075.

Zeuzem S, Yoshida EM, Benhamou Y, Pianko S, Bain VG, Shouval D, et al.

Albinterferon alfa-2b dosed every two or four weeks in interferon-naive

patients with genotype 1 chronic hepatitis C. Hepatology. 2008;48(2):407–17.

doi:10.1002/hep.22403.

Zeuzem S, Sulkowski MS, Lawitz EJ, Rustgi VK, Rodriguez-Torres M,

Bacon BR, et al. Albinterferon Alfa-2b was not inferior to pegylated

interferon-alpha in a randomized trial of patients with chronic hepatitis

C virus genotype 1. Gastroenterology. 2010;139(4):1257–66. doi:10.1053/j.

gastro.2010.06.066.

Colvin RA, Tanwandee T, Piratvisuth T, Thongsawat S, Hui AJ, Zhang H, et al.

Randomized, controlled pharmacokinetic and pharmacodynamic evaluation

of albinterferon in patients with chronic hepatitis B infection. J

Gastroenterol Hepatol. 2015;30(1):184–91. doi:10.1111/jgh.12671.

Prescription Drug Information ISe. http://www.drugs.com/history/zalbin.html.

Accessed 13 Nov 2015.

Kratz F. DOXO-EMCH (INNO-206): the first albumin-binding prodrug of

doxorubicin to enter clinical trials. Expert Opin Investig Drugs. 2007;16(6):855–66.

doi:10.1517/13543784.16.6.855.

Kratz F. A clinical update of using albumin as a drug vehicle - a commentary.

J Control Release. 2014;190:331–6. doi:10.1016/j.jconrel.2014.03.013.

Kratz F, Warnecke A, Scheuermann K, Stockmar C, Schwab J, Lazar P, et al.

Probing the cysteine-34 position of endogenous serum albumin with thiolbinding

doxorubicin derivatives. Improved efficacy of an acid-sensitive

doxorubicin derivative with specific albumin-binding properties compared

to that of the parent compound. J Med Chem. 2002;45(25):5523–33.

Kratz F, Muller-Driver R, Hofmann I, Drevs J, Unger C. A novel

macromolecular prodrug concept exploiting endogenous serum albumin as

a drug carrier for cancer chemotherapy. J Med Chem. 2000;43(7):1253–6.

Chawla SP, Papai Z, Mukhametshina G, Sankhala K, Vasylyev L, Fedenko A,

et al. First-Line Aldoxorubicin vs Doxorubicin in Metastatic or Locally

Advanced Unresectable Soft-Tissue Sarcoma: A Phase 2b Randomized Clinical

Trial. JAMA Oncol. 2015;1(9):1271–80. doi:10.1001/jamaoncol.2015.3101.

CytRx. http://www.cytrx.com/aldoxorubicin. Accessed 13 Nov 2015.

Lau S, Graham B, Cao N, Boyd BJ, Pouton CW, White PJ. Enhanced

extravasation, stability and in vivo cardiac gene silencing via in situ siRNAalbumin

conjugation. Mol Pharm. 2012;9(1):71–80. doi:10.1021/mp2002522.

Ehrlich GK, Michel H, Truitt T, Riboulet W, Pop-Damkov P, Goelzer P, et al.

Preparation and characterization of albumin conjugates of a truncated peptide

YY analogue for half-life extension. Bioconjug Chem. 2013;24(12):2015–24.

doi:10.1021/bc400340z.

Stehle G, Sinn H, Wunder A, Schrenk HH, Schutt S, Maier-Borst W, et al. The

loading rate determines tumor targeting properties of methotrexatealbumin

conjugates in rats. Anti Cancer Drugs. 1997;8(7):677–85.

Hartung G, Stehle G, Sinn H, Wunder A, Schrenk HH, Heeger S, et al. Phase I

trial of methotrexate-albumin 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. 1999;5(4):753–9.

Bolling C, Graefe T, Lubbing C, Jankevicius F, Uktveris S, Cesas A, et al. Phase

II study of MTX-HSA in combination with cisplatin as first line treatment in

patients with advanced or metastatic transitional cell carcinoma. Investig

New Drugs. 2006;24(6):521–7. doi:10.1007/s10637-006-8221-6.

Tumey LN, Charati M, He T, Sousa E, Ma D, Han X, et al. Mild method for

succinimide hydrolysis on ADCs: impact on ADC potency, stability, exposure,

and efficacy. Bioconjug Chem. 2014;25(10):1871–80. doi:10.1021/bc500357n.

Fontaine SD, Reid R, Robinson L, Ashley GW, Santi DV. Long-term

stabilization of maleimide-thiol conjugates. Bioconjug Chem. 2015;26(1):

–52. doi:10.1021/bc5005262.

Andersen JT, Dalhus B, Viuff D, Ravn BT, Gunnarsen KS, Plumridge A, et al.

Extending serum half-life of albumin by engineering neonatal Fc

receptor (FcRn) binding. J Biol Chem. 2014;289(19):13492–502.

doi:10.1074/jbc.M114.549832.

Elsadek B, Kratz F. Impact of albumin on drug delivery–new applications on the

horizon. J Control Release. 2012;157(1):4–28. doi:10.1016/j.jconrel.2011.09.069.

Home P, Kurtzhals P. Insulin detemir: from concept to clinical experience.

Expert Opin Pharmacother. 2006;7(3):325–43. doi:10.1517/14656566.7.3.325.

Wunder A, Muller-Ladner U, Stelzer EH, Funk J, Neumann E, Stehle G, et al.

Albumin-based drug delivery as novel therapeutic approach for rheumatoid

arthritis. J Immunol. 2003;170(9):4793–801.

Larsen et al. Molecular and Cellular Therapies (2016) 4:3 Page 11 of 12

Stehle G, Wunder A, Sinn H, Schrenk HH, Schutt S, Frei E, et al.

Pharmacokinetics of methotrexate-albumin conjugates in tumor-bearing

rats. Anti Cancer Drugs. 1997;8(9):835–44.

Clinical Trials NCT01706835. https://www.clinicaltrials.gov/ct2/ct2/show/

NCT01706835?1016term=aldoxorubicin&rank=5. Accessed Nov 13 2015.

Baggio LL, Huang Q, Cao X, Drucker DJ. An albumin-exendin-4

conjugate engages central and peripheral circuits regulating murine

energy and glucose homeostasis. Gastroenterology. 2008;134(4):1137–47.

doi:10.1053/j.gastro.2008.01.017.

Leger R, Thibaudeau K, Robitaille M, Quraishi O, van Wyk P, BousquetGagnon

N, et al. Identification of CJC-1131-albumin bioconjugate as a

stable and bioactive GLP-1(7–36) analog. Bioorg Med Chem Lett.

;14(17):4395–8. doi:10.1016/j.bmcl.2004.06.066.

Clinical Trials NCT00638716. https://www.clinicaltrials.gov/ct2/ct2/show/

NCT00638716?term=1026conjuchem&rank=2. Accessed Nov 18 2015.

ConjuChem. http://www.conjuchem.com/pipeline/cjc-1134-pc.

Accessed Nov 18 2015.

Poole RM, Nowlan ML. Albiglutide: first global approval. Drugs. 2014;74(8):929–38.

doi:10.1007/s40265-014-0228-2.

Baggio LL, Huang Q, Brown TJ, Drucker DJ. A recombinant human

glucagon-like peptide (GLP)-1-albumin protein (albugon) mimics

peptidergic activation of GLP-1 receptor-dependent pathways coupled

with satiety, gastrointestinal motility, and glucose homeostasis. Diabetes.

;53(9):2492–500.

Glaxo Smith Kline. http://www.gsk.com/en-gb/media/press-releases/2014/

gsk-receives-us-approval-for-once-weekly-type-2-diabetes-treatmenttanzeum-albiglutide/.

Accessed Nov 13 2015.

Golor G, Bensen-Kennedy D, Haffner S, Easton R, Jung K, Moises T, et al.

Safety and pharmacokinetics of a recombinant fusion protein linking

coagulation factor VIIa with albumin in healthy volunteers. J Thromb

Haemost. 2013;11(11):1977–85. doi:10.1111/jth.12409.

Schulte S. Use of albumin fusion technology to prolong the half-life

of recombinant factor VIIa. Thromb Res. 2008;122 Suppl 4:S14–9.

doi:10.1016/S0049-3848(08)70029-X.

Weimer T, Wormsbacher W, Kronthaler U, Lang W, Liebing U, Schulte S.

Prolonged in-vivo half-life of factor VIIa by fusion to albumin. Thromb

Haemost. 2008;99(4):659–67. doi:10.1160/TH07-08-0525.

Clinical Trials NCT01542619. https://www.clinicaltrials.gov/ct2/ct2/show/

NCT01542619?1050term=albumin+fusion+VIIa&rank=1. Accessed Nov 18 2015.

Clinical Trials NCT01496274. https://www.clinicaltrials.gov/ct2/ct2/show/

NCT01496274?1052term=rIX-FP&rank=3. Accessed Dec 2 2015.

http://www.drugs.com. http://www.drugs.com/nda/zalbin_101005.html.

Accessed Nov 18 2015.

Abraxane. http://www.abraxane.com. Accessed Nov 13 2015.

Published
2018-11-16
Section
Review