Polyethylene glycol (PEG) at the moment is considered the leading polymer for protein conjugation in view of its unique properties, as well as to its low toxicity in humans, qualities which have been confirmed by its extensive use in clinical practice. Other polymers that are safe, biodegradable and custom-designed have, nevertheless, also been investigated as potential candidates for protein conjugation. This review will focus on natural polymers and synthetic linear polymers that have been used for protein delivery and the results associated with their use. Genetic fusion approaches for the preparation of protein-polypeptide conjugates will be also reviewed and compared with the best known chemical conjugation ones.
References
[1]
Biosimilars and Follow-on Biologics Report: The Global Outlook 2010–2025. Visiongain Ltd.: London, UK, 2010. Available online: http://www.visiongain.com/Report/474/Biosimilars-and-Follow-On-Biologics-Global-Market-Outlook-2010-2025 (accessed on 9 January 2014).
[2]
Abuchowski, A.; van Es, T.; Palczuk, N.; Davis, F. Alteration of immunological properties of bovine serum albumin by covalent attachment of polyethylene glycol. J. Biol. Chem. 1977, 252, 3578–3581.
[3]
Abuchowski, A.; McCoy, J.R.; Palczuk, N.C.; van Es, T.; Davis, F.F. Effect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase. J. Biol. Chem. 1977, 252, 3582–3586.
[4]
Torchilin, V.; Voronkov, Y.I.; Mazaev, A. Use of immobilized streptokinase (Streptodekaza) for thrombosis treatment. Ter. Arkhiv 1982, 54, 21–26.
[5]
Pasut, G.; Veronese, F.M. State of the art in PEGylation: The great versatility achieved after forty years of research. J. Control. Release 2012, 161, 461–472, doi:10.1016/j.jconrel.2011.10.037.
[6]
Webster, R.; Didier, E.; Harris, P.; Siegel, N.; Stadler, J.; Tilbury, L.; Smith, D. PEGylated proteins: Evaluation of their safety in the absence of definitive metabolism studies. Drug Metab. Dispos. 2007, 35, 9–16.
[7]
Harris, J.M.; Chess, R.B. Effect of pegylation on pharmaceuticals. Nat. Rev. Drug Discov. 2003, 2, 214–221, doi:10.1038/nrd1033.
[8]
Manjula, B.; Tsai, A.; Upadhya, R.; Perumalsamy, K.; Smith, P.; Malavalli, A.; Vandegriff, K.; Winslow, R.; Intaglietta, M.; Prabhakaran, M. Site-specific PEGylation of hemoglobin at Cys-93(β): Correlation between the colligative properties of the PEGylated protein and the length of the conjugated PEG chain. Bioconjug. Chem. 2003, 14, 464–472, doi:10.1021/bc0200733.
[9]
Kinstler, O.; Moulinex, G.; Treheit, M.; Ladd, D.; Gegg, C. Mono-N-terminal poly(ethylene glycol)-protein conjugates. Adv. Drug Deliv. Rev. 2002, 54, 477–485, doi:10.1016/S0169-409X(02)00023-6.
[10]
Basu, A.; Yang, K.; Wang, M.; Liu, S.; Chintala, R.; Palm, T.; Zhao, H.; Peng, P.; Wu, D.; Zhang, Z. Structure-function engineering of interferon-β-1b for improving stability, solubility, potency, immunogenicity, and pharmacokinetic properties by site-selective mono-PEGylation. Bioconjug. Chem. 2006, 17, 618–630, doi:10.1021/bc050322y.
[11]
Veronese, F.M.; Mero, A.; Caboi, F.; Sergi, M.; Marongiu, C.; Pasut, G. Site-specific pegylation of G-CSF by reversible denaturation. Bioconjug. Chem. 2007, 18, 1824–1830, doi:10.1021/bc070123+.
[12]
Weir, N.; Athwal, D.; Brown, D.; Foulkes, R.; Kollias, G.; Nesbitt, A.; Popplewell, A.; Spitali, M.; Stephens, S. A new generation of high-affinity humanized PEGylated fab fragment anti-tumor necrosis factor-α monoclonal antibodies. Therapy 2006, 3, 535–545.
[13]
Shaunak, S.; Godwin, A.; Choi, J.; Balan, S.; Pedone, E.; Vijayarangam, D.; Heidelberger, S.; Teo, I.; Zloh, M.; Brocchini, S. Site-specific PEGylation of native disulfide bonds in therapeutic proteins. Nat. Chem. Biol. 2006, 2, 312–313, doi:10.1038/nchembio786.
[14]
Mero, A.; Schiavon, M.; Veronese, F.M.; Pasut, G. A new method to increase selectivity of transglutaminase mediated PEGylation of salmon calcitonin and human growth hormone. J. Control. Release 2011, 154, 27–34, doi:10.1016/j.jconrel.2011.04.024.
[15]
DeFrees, S.; Wang, Z.; Xing, R.; Scott, A.E.; Wang, J.; Zopf, D.; Gouty, D.L.; Sjoberg, E.R.; Panneerselvam, K.; Brinkman-Van, der Linden; Els, C.M. GlycoPEGylation of recombinant therapeutic proteins produced in Escherichia coli. Glycobiology 2006, 16, 833–843, doi:10.1093/glycob/cwl004.
[16]
Popp, M.W.; Dougan, S.K.; Chuang, T.; Spooner, E.; Ploegh, H.L. Sortase-catalyzed transformations that improve the properties of cytokines. Proc. Natl. Acad. Sci. USA 2011, 108, 3169–3174, doi:10.1073/pnas.1016863108.
[17]
Zhao, H.; Yang, K.; Martinez, A.; Basu, A.; Chintala, R.; Liu, H.; Janjua, A.; Wang, M.; Filpula, D. Linear and branched bicin linkers for releasable PEGylation of macromolecules: Controlled release in vivo and in vitro from mono-and multi-PEGylated proteins. Bioconjug. Chem. 2006, 17, 341–351, doi:10.1021/bc050270c.
[18]
Greenwald, R.B.; Yang, K.; Zhao, H.; Conover, C.D.; Lee, S.; Filpula, D. Controlled release of proteins from their poly(ethylene glycol) conjugates: Drug delivery systems employing 1, 6-elimination. Bioconjug. Chem. 2003, 14, 395–403, doi:10.1021/bc025652m.
[19]
Greenwald, R.B.; Choe, Y.H.; Conover, C.D.; Shum, K.; Wu, D.; Royzen, M. Drug delivery systems based on trimethyl lock lactonization: Poly(ethylene glycol) prodrugs of amino-containing compounds. J. Med. Chem. 2000, 43, 475–487, doi:10.1021/jm990498j.
[20]
Tsubery, H.; Mironchik, M.; Fridkin, M.; Shechter, Y. Prolonging the action of protein and peptide drugs by a novel approach of reversible polyethylene glycol modification. J. Biol. Chem. 2004, 279, 38118–38124, doi:10.1074/jbc.M405155200.
[21]
Wylie, D.C.; Voloch, M.; Lee, S.; Liu, Y.; Cannon-Carlson, S.; Cutler, C.; Pramanik, B. Carboxyalkylated histidine is a pH-dependent product of pegylation with SC-PEG. Pharm. Res. 2001, 18, 1354–1360, doi:10.1023/A:1013006515587.
[22]
Pasut, G.; Caboi, F.; Schrepfer, R.; Tonon, G.; Schiavon, O.; Veronese, F. New active poly(ethylene glycol) derivative for amino coupling. React. Funct. Polym. 2007, 67, 529–539, doi:10.1016/j.reactfunctpolym.2007.03.005.
[23]
Pasut, G.; Mero, A.; Caboi, F.; Scaramuzza, S.; Sollai, L.; Veronese, F.M. A new PEG-β-alanine active derivative for releasable protein conjugation. Bioconjug. Chem. 2008, 19, 2427–2431, doi:10.1021/bc800281s.
[24]
Mueller, C.; Capelle, M.A.; Arvinte, T.; Seyrek, E.; Borchard, G. Noncovalent pegylation by dansyl-poly(ethylene glycol)s as a new means against aggregation of salmon calcitonin. J. Pharm. Sci. 2011, 100, 1648–1662, doi:10.1002/jps.22401.
[25]
Mueller, C.; Capelle, M.A.; Arvinte, T.; Seyrek, E.; Borchard, G. Tryptophan-mPEGs: Novel excipients that stabilize salmon calcitonin against aggregation by non-covalent PEGylation. Eur. J. Pharm. Biopharm. 2011, 79, 646–657, doi:10.1016/j.ejpb.2011.06.003.
[26]
Mero, A.; Ishino, T.; Chaiken, I.; Veronese, F.M.; Pasut, G. Multivalent and flexible PEG-nitrilotriacetic acid derivatives for non-covalent protein pegylation. Pharm. Res. 2011, 28, 2412–2421, doi:10.1007/s11095-011-0468-8.
[27]
Liu, M.; Tirino, P.; Radivojevic, M.; Phillips, D.J.; Gibson, M.I.; Leroux, J.; Gauthier, M.A. Molecular sieving on the surface of a protein provides protection without loss of activity. Adv. Funct. Mater. 2012, 23, 2007–2015.
[28]
Miyaji, Y.; Kasuya, Y.; Furuta, Y.; Kurihara, A.; Takahashi, M.; Ogawara, K.; Izumi, T.; Okazaki, O.; Higaki, K. Novel comb-shaped PEG modification enhances the osteoclastic inhibitory effect and bone delivery of osteoprotegerin after intravenous administration in ovariectomized rats. Pharm. Res. 2012, 29, 3143–3155, doi:10.1007/s11095-012-0807-4.
Armstrong, J.K.; Hempel, G.; Koling, S.; Chan, L.S.; Fisher, T.; Meiselman, H.J.; Garratty, G. Antibody against poly(ethylene glycol) adversely affects PEG-asparaginase therapy in acute lymphoblastic leukemia patients. Cancer 2007, 110, 103–111, doi:10.1002/cncr.22739.
[31]
Sherman, M.R.; Saifer, M.G.; Perez-Ruiz, F. PEG-Uricase in the management of treatment-resistant gout and hyperuricemia. Adv. Drug Deliv. Rev. 2008, 60, 59–68, doi:10.1016/j.addr.2007.06.011.
[32]
Leger, R.M.; Arndt, P.; Garratty, G.; Armstrong, J.K.; Meiselman, H.J.; Fisher, T.C. Normal donor sera can contain antibodies to polyethylene glycol (PEG). Transfusion 2001, 41, 29S.
[33]
Fisher, T.C.; Armstrong, J.K.; Wenby, R.B.; Meiselman, H.J.; Leger, R.; Garratty, G. Isolation and identification of a human antibody to polyethylene glycol (abstract). Blood 2003, 102, 559A.
[34]
Bendele, A.; Seely, J.; Richey, C.; Sennello, G.; Shopp, G. Short communication: Renal tubular vacuolation in animals treated with polyethylene-glycol-conjugated proteins. Toxicol. Sci. 1998, 42, 152–157, doi:10.1093/toxsci/42.2.152.
[35]
Conover, C.; Lejeune, L.; Linberg, R.; Shum, K.; Shorr, R.G. Transitional vacuole formation following a bolus infusion of PEG-hemoglobin in the rat. Artif. Cell. Blood Sub. 1996, 24, 599–611, doi:10.3109/10731199609118885.
[36]
Garay, R.P.; El-Gewely, R.; Armstrong, J.K.; Garratty, G.; Richette, P. Antibodies against polyethylene glycol in healthy subjects and in patients treated with PEG-conjugated agents. Expert Opin. Drug Del. 2012, 9, 1319–1323, doi:10.1517/17425247.2012.720969.
[37]
Ganson, N.; Kelly, S.; Scarlett, E.; Sundy, J.; Hershfield, M. Control of hyperuricemia in subjects with refractory gout, and induction of antibody against poly(ethylene glycol) (PEG), in a phase I trial of subcutaneous PEGylated urate oxidase. Arthritis Res. Ther. 2005, doi:10.1186/ar1861.
[38]
Zhang, C.; Fan, K.; Ma, X.; Wei, D. Impact of large aggregated uricases and PEG diol on accelerated blood clearance of PEGylated canine uricase. PLoS One 2012, 7, e39659, doi:10.1371/journal.pone.0039659.
[39]
Abu Lila, A.S.; Kiwada, H.; Ishida, T. The accelerated blood clearance (ABC) phenomenon: Clinical challenge and approaches to manage. J. Control. Release 2013, 172, 38–47, doi:10.1016/j.jconrel.2013.07.026.
[40]
Schellekens, H.; Hennink, W.E.; Brinks, V. The immunogenicity of polyethylene glycol: Facts and fiction. Pharm. Res. 2013, 30, 1729–1734, doi:10.1007/s11095-013-1067-7.
[41]
Jev？evar, S.; Kunstelj, M.; Porekar, V.G. PEGylation of therapeutic proteins. Biotechnol. J. 2010, 5, 113–128, doi:10.1002/biot.200900218.
[42]
Pasut, G.; Veronese, F.M. PEG conjugates in clinical development or use as anticancer agents: An overview. Adv. Drug Deliv. Rev. 2009, 61, 1177–1188, doi:10.1016/j.addr.2009.02.010.
[43]
Mehvar, R. Recent trends in the use of polysaccharides for improved delivery of therapeutic agents: Pharmacokinetic and pharmacodynamic perspectives. Curr. Pharm. Biotechnol. 2003, 4, 283–302, doi:10.2174/1389201033489685.
[44]
Mehvar, R. Dextrans for targeted and sustained delivery of therapeutic and imaging agents. J. Control. Release 2000, 69, 1–25.
[45]
Larsen, C. Dextran prodrugs—Structure and stability in relation to therapeutic activity. Adv. Drug Deliv. Rev. 1989, 3, 103–154, doi:10.1016/0169-409X(89)90006-9.
[46]
Walker, G.J. Dextrans. In Biochemistry of Carbohydrates; Manners, D.J., Ed.; University Park Press: Baltimore, MD, USA, 1978; Volume 16, pp. 75–126.
[47]
Mehvar, R.; Shepard, T.L. Molecular-weight-dependent pharmacokinetics of fluorescein-labeled dextrans in rats. J. Pharm. Sci. 1992, 81, 908–912, doi:10.1002/jps.2600810914.
[48]
Vercauteren, R.; Bruneel, D.; Schacht, E.; Duncan, R. Effect of the chemical modification of dextran on the degradation by dextranase. J. Bioact. Compat. Pol. 1990, 5, 4–15, doi:10.1177/088391159000500102.
[49]
Schacht, E.; Vercauteren, R.; Vansteenkiste, S. Some aspects of the application of dextran in prodrug design. J. Bioact. Compat. Pol. 1988, 3, 72–80, doi:10.1177/088391158800300107.
[50]
Wileman, T.E. Properties of asparaginase-dextran conjugates. Adv. Drug Deliv. Rev. 1991, 6, 167–180, doi:10.1016/0169-409X(91)90039-F.
[51]
Wileman, T.E.; Foster, R.L.; Elliott, P.N. Soluble asparaginase-dextran conjugates show Increased circulatory persistence and lowered antigen reactivity. J. Pharm. Pharmacol. 1986, 38, 264–271, doi:10.1111/j.2042-7158.1986.tb04564.x.
[52]
Melton, R.G.; Wiblin, C.N.; Foster, R.L.; Sherwood, R.F. Covalent linkage of carboxypeptidase G2 to soluble dextrans: I. Properties of conjugates and effects on plasma persistence in mice. Biochem. Pharmacol. 1987, 36, 105–112, doi:10.1016/0006-2952(87)90387-X.
[53]
Molteni, L. Dextrans as Drug Carriers. In Drug Carriers in Biology and Medicine; Gregoriadis, G., Ed.; Academic Press: New York, NY, USA, 1979; pp. 107–125.
[54]
Yasuda, Y.; Fujita, T.; Takakura, Y.; Hashida, M.; Sezaki, H. Biochemical and biopharmaceutical properties of macromolecular conjugates of uricase with dextran and polyethylene glycol. Chem. Pharm. Bull. (Tokyo) 1990, 38, 2053–2056, doi:10.1248/cpb.38.2053.
[55]
Fujita, T.; Nishikawa, M.; Tamaki, C.; Takakura, Y.; Hashida, M.; Sezaki, H. Targeted delivery of human recombinant superoxide dismutase by chemical modification with mono-and polysaccharide derivatives. J. Pharmacol. Exp. Ther. 1992, 263, 971–978.
[56]
Baudy？, M.; Letourneur, D.; Liu, F.; Mix, D.; Jozefonvicz, J.; Kim, S.W. Extending insulin action in vivo by conjugation to carboxymethyl dextran. Bioconjug. Chem. 1998, 9, 176–183, doi:10.1021/bc970180a.
[57]
Caron, A.; Menu, P.; Faivre-Fiorina, B.; Labrude, P.; Vigneron, C. The effects of stroma-free and dextran-conjugated hemoglobin on hemodynamics and carotid blood flow in hemorrhaged guinea pigs. Art. Cell. Blood Sub. 1999, 27, 49–64, doi:10.3109/10731199909117483.
[58]
Faivre, B.; Labaeye, V.; Menu, P.; Labrude, P.; Vigneron, C. Assessment of dextran 10-benzene-tetracarboxylate-hemoglobin, an oxygen carrier, using guinea pig isolated bowel model. Art. Cell. Blood Sub. 1995, 23, 495–504, doi:10.3109/10731199509117965.
[59]
Hreczuk-Hirst, D.; Jain, S.; Genkin, D.; Laing, P.; Gregoriadis, G. Preparation and Properties of Polysialylated Interferon-α-2b. In Proceedings of the AAPS Annual Meeting, Toronto, ON, Canada, 10–14 November, 2002. M1056.
[60]
Gregoriadis, G.; McCormack, B.; Wang, Z.; Lifely, R. Polysialic acids: Potential in drug delivery. FEBS Lett. 1993, 315, 271–276, doi:10.1016/0014-5793(93)81177-2.
[61]
Gregoriadis, G.; Jain, S.; Papaioannou, I.; Laing, P. Improving the therapeutic efficacy of peptides and proteins: A role for polysialic acids. Int. J. Pharm. 2005, 300, 125–130, doi:10.1016/j.ijpharm.2005.06.007.
[62]
Jain, S.; Hreczuk-Hirst, D.H.; McCormack, B.; Mital, M.; Epenetos, A.; Laing, P.; Gregoriadis, G. Polysialylated insulin: Synthesis, characterization and biological activity in vivo. Biochim. Biophys. Acta 2003, 1622, 42–49, doi:10.1016/S0304-4165(03)00116-8.
[63]
Epenetos, A.; Hreczuk-Hirst, D.; McCormack, B.; Gregoriadis, G. Polysialylated proteins: A potential role in cancer therapy. Clin. Pharm. 2002, 21, 2186.
[64]
Gregoriadis, G.; Fernandes, A.; Mital, M.; McCormack, B. Polysialic acids: Potential in improving the stability and pharmacokinetics of proteins and other therapeutics. Cell. Mol. Life Sci. 2000, 57, 1964–1969, doi:10.1007/PL00000676.
[65]
Fernandes, A.I.; Gregoriadis, G. The effect of polysialylation on the immunogenicity and antigenicity of asparaginase: Implication in its pharmacokinetics. Int. J. Pharm. 2001, 217, 215–224, doi:10.1016/S0378-5173(01)00603-2.
[66]
Constantinou, A.; Epenetos, A.; Hreczuk-Hirst, D.; Jain, S.; Wright, M.; Chester, K.; Deonarain, M. Site-specific polysialylation of an antitumor single-chain Fv fragment. Bioconjug. Chem. 2009, 20, 924–931, doi:10.1021/bc8005122.
[67]
Lindhout, T.; Iqbal, U.; Willis, L.M.; Reid, A.N.; Li, J.; Liu, X.; Moreno, M.; Wakarchuk, W.W. Site-specific enzymatic polysialylation of therapeutic proteins using bacterial enzymes. Proc. Natl. Acad. Sci. USA 2011, 108, 7397–7402.
[68]
Evered, D.; Whelan, J. The Biology of Hyaluronan; Wiley & Sons: Chichester, UK, 1989.
[69]
Almond, A. Hyaluronan. Cell. Mol. Life Sci. 2007, 64, 1591–1596, doi:10.1007/s00018-007-7032-z.
[70]
Laurent, T.C.; Fraser, J.R. Hyaluronan. FASEB J. 1992, 6, 2397–2404.
[71]
Saravanakumar, G.; Choi, K.Y.; Yoon, H.Y.; Kim, K.; Park, J.H.; Kwon, I.C.; Park, K. Hydrotropic hyaluronic acid conjugates: Synthesis, characterization, and implications as a carrier of paclitaxel. Int. J. Pharm. 2010, 394, 154–161, doi:10.1016/j.ijpharm.2010.04.041.
Yang, J.; Park, K.; Jung, H.; Kim, H.; Hong, S.W.; Yoon, S.K.; Hahn, S.K. Target specific hyaluronic acid–interferon alpha conjugate for the treatment of hepatitis C virus infection. Biomaterials 2011, 32, 8722–8729, doi:10.1016/j.biomaterials.2011.07.088.
[74]
Mero, A.; Pasqualin, M.; Campisi, M.; Renier, D.; Pasut, G. Conjugation of hyaluronan to proteins. Carbohydr. Polym. 2013, 92, 2163–2170, doi:10.1016/j.carbpol.2012.11.090.
[75]
D’Este, M.; Renier, D.; Pasut, G.; Rosato, A. Process for the Synthesis of Conjugates of Glycosaminoglycanes (GAG) with Biologically Active Molecules, Polymeric Conjugates and Relative Uses Thereof. WO2010145821 A1, 23 December 2010.
[76]
Campisi, M.; Mero, A. Hyaluronic acid as polymeric carrier of drugs and proteins. Polymers 2014. in press.
[77]
Ferguson, E.L.; Richardson, S.C.; Duncan, R. Studies on the mechanism of action of dextrin—Phospholipase A2 and its suitability for use in combination therapy. Mol. Pharm. 2010, 7, 510–521, doi:10.1021/mp900232a.
[78]
Duncan, R.; Gilbert, H.; Carbajo, R.; Vicent, M. Polymer masked-unmasked protein therapy (PUMPT) 1: Bioresponsive dextrin-trypsin and-MSH conjugates designed for α-amylase activation. Biomacromolecules 2008, 9, 1146–1154, doi:10.1021/bm701073n.
[79]
Hardwicke, J.T.; Hart, J.; Bell, A.; Duncan, R.; Thomas, D.W.; Moseley, R. The Effect of dextrin–rhEGF on the healing of full-thickness, excisional wounds in the (db/db) diabetic mouse. J. Control. Release 2011, 152, 411–417, doi:10.1016/j.jconrel.2011.03.016.
[80]
Hardwicke, J.; Moseley, R.; Stephens, P.; Harding, K.; Duncan, R.; Thomas, D.W. Bioresponsive dextrin？rhEGF conjugates: In vitro evaluation in models relevant to its proposed use as a treatment for chronic wounds. Mol. Pharm. 2010, 7, 699–707, doi:10.1021/mp9002656.
[81]
Besheer, A.; Hertel, T.C.; Kressler, J.; M？der, K.; Pietzsch, M. Enzymatically catalyzed HES conjugation using microbial transglutaminase: Proof of feasibility. J. Pharm. Sci. 2009, 98, 4420–4428, doi:10.1002/jps.21675.
[82]
Besheer, A.; Hause, G.; Kressler, J.; M？der, K. Hydrophobically modified hydroxyethyl starch: Synthesis, characterization, and aqueous self-assembly into nano-sized polymeric micelles and vesicles. Biomacromolecules 2007, 8, 359–367, doi:10.1021/bm0609487.
[83]
Schubert, S.; Autenrieth, I.B. Conjugation of hydroxyethyl starch to desferrioxamine (DFO) modulates the dual role of DFO in yersinia enterocolitica infection. Clin. Diagn. Lab. Immunol. 2000, 7, 457–462.
[84]
Zander, N.; Conradt, H.; Eichner, W. Method of Producing Hydroxyalkyl Starch Derivatives. WO2004024776, 25 March 2004.
[85]
Conradt, H.S.; Grabenhorst, E.; Nimtz, M.; Zander, N.; Frank, R.; Eichner, W. HASylated Polypeptides, especially HASylated Erythropoietin. WO2004024761 A1, 25 March 2004.
[86]
Zarychanski, R.; Abou-Setta, A.M.; Turgeon, A.F.; Houston, B.L.; McIntyre, L.; Marshall, J.C.; Fergusson, D.A. Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically Ill patients requiring volume resuscitationa systematic review and meta-analysis hydroxyethyl starch and outcomes in critically Ill. JAMA 2013, 309, 678–688, doi:10.1001/jama.2013.430.
[87]
Perel, P.; Roberts, I.; Pearson, M. Colloids versus crystalloids for fluid resuscitation in critically Ill patients. Cochrane Database Syst. Rev. 2007, 4, CD000567.
[88]
PRAC Recommends Suspending Marketing Authorizations for Infusion Solutions Containing Hydroxyethyl Starch. Available online: http://www.ema.europa.eu/ema/index.jsp?curl=pages/ news_and_events/news/2013/06/news_detail_001814.jsp&mid=WC0b01ac058004d5c1 (accessed on 25 November 2013).
[89]
Zalipsky, S.; Hansen, C.B.; Oaks, J.M.; Allen, T.M. Evaluation of blood clearance rates and biodistribution of poly(2-oxazoline)-grafted liposomes. J. Pharm. Sci. 1996, 85, 133–137, doi:10.1021/js9504043.
[90]
Hoogenboom, R. Poly(2-oxazoline)s: A polymer class with numerous potential applications. Angew. Chem. Int. Ed. 2009, 48, 7978–7994, doi:10.1002/anie.200901607.
[91]
Mero, A.; Pasut, G.; Via, L.D.; Fijten, M.W.; Schubert, U.S.; Hoogenboom, R.; Veronese, F.M. Synthesis and characterization of poly(2-ethyl 2-oxazoline)-conjugates with proteins and drugs: Suitable alternatives to PEG-conjugates? J. Control. Release 2008, 125, 87–95, doi:10.1016/j.jconrel.2007.10.010.
[92]
Goddard, P.; Hutchinson, L.E.; Brown, J.; Brookman, L.J. Soluble polymeric carriers for drug delivery: Part 2. Preparation and in vivo behaviour of N-acylethylenimine copolymers. J. Control. Release 1989, 10, 5–16, doi:10.1016/0168-3659(89)90013-8.
[93]
Miyamoto, M.; Naka, K.; Tokumizu, M.; Saegusa, T. End capping of growing species of poly(2-oxazoline) with carboxylic acid: A novel and convenient route to prepare vinyl-and carboxy-terminated macromonomers. Macromolecules 1989, 22, 1604–1607, doi:10.1021/ma00194a016.
[94]
Einzmann, M.; Binder, W.H. Novel functional initiators for oxazoline polymerization. J. Polym. Sci. A 2001, 39, 2821–2831, doi:10.1002/pola.1262.
[95]
Jordan, R.; Ulman, A. Surface initiated living cationic polymerization of 2-oxazolines. J. Am. Chem. Soc. 1998, 120, 243–247, doi:10.1021/ja973392r.
[96]
Kobayashi, S.; Masuda, E.; Shoda, S.; Shimano, Y. Synthesis of acryl-and methacryl-type macromonomers and telechelics by utilizing living polymerization of 2-oxazolines. Macromolecules 1989, 22, 2878–2884, doi:10.1021/ma00197a002.
[97]
Kobayashi, S.; Iijima, S.; Igarashi, T.; Saegusa, T. Synthesis of a nonionic polymer surfactant from cyclic imino ethers by the initiator method. Macromolecules 1987, 20, 1729–1734, doi:10.1021/ma00174a001.
[98]
Mero, A.; Fang, Z.; Pasut, G.; Veronese, F.M.; Viegas, T.X. Selective conjugation of poly(2-ethyl 2-oxazoline) to granulocyte colony stimulating factor. J. Control. Release 2012, 159, 353–361, doi:10.1016/j.jconrel.2012.02.025.
[99]
Gaertner, F.C.; Luxenhofer, R.; Blechert, B.; Jordan, R.; Essler, M. Synthesis, biodistribution and excretion of radiolabeled poly(2-alkyl-2-oxazoline)s. J. Control. Release 2007, 119, 291–300, doi:10.1016/j.jconrel.2007.02.015.
Tong, J.; Luxenhofer, R.; Yi, X.; Jordan, R.; Kabanov, A.V. Protein modification with amphiphilic block copoly(2-oxazoline)s as a new platform for enhanced cellular delivery. Mol. Pharm. 2010, 7, 984–992, doi:10.1021/mp100102p.
Schmidt, S.R. Fusion-proteins as biopharmaceuticals—Applications and challenges. Curr. Opin. Drug Discov. Devel. 2009, 12, 284–295.
[105]
Subramanian, G.M.; Fiscella, M.; Lamousé-Smith, A.; Zeuzem, S.; McHutchison, J.G. Albinterferon α-2b: A genetic fusion protein for the treatment of chronic hepatitis C. Nat. Biotechnol. 2007, 25, 1411–1419, doi:10.1038/nbt1364.
[106]
Schellenberger, V.; Wang, C.; Geething, N.C.; Spink, B.J.; Campbell, A.; To, W.; Scholle, M.D.; Yin, Y.; Yao, Y.; Bogin, O. A recombinant polypeptide extends the in vivo half-life of peptides and proteins in a tunable manner. Nat. Biotechnol. 2009, 27, 1186–1190, doi:10.1038/nbt.1588.
[107]
Cleland, J.L.; Geething, N.C.; Moore, J.A.; Rogers, B.C.; Spink, B.J.; Wang, C.; Alters, S.E.; Stemmer, W.P.; Schellenberger, V. A novel long-acting human growth hormone fusion protein (vrs-317): Enhanced in vivo potency and half-life. J. Pharm. Sci. 2012, 101, 2744–2754, doi:10.1002/jps.23229.
[108]
Geething, N.C.; To, W.; Spink, B.J.; Scholle, M.D.; Wang, C.; Yin, Y.; Yao, Y.; Schellenberger, V.; Cleland, J.L.; Stemmer, W.P. Gcg-XTEN: An improved glucagon capable of preventing hypoglycemia without increasing baseline blood glucose. PLoS One 2010, 5, e10175, doi:10.1371/journal.pone.0010175.
[109]
Schlapschy, M.; Theobald, I.; Mack, H.; Schottelius, M.; Wester, H.; Skerra, A. Fusion of a recombinant antibody fragment with a homo-amino-acid polymer: Effects on biophysical properties and prolonged plasma half-life. Protein Eng. Des. Sel. 2007, 20, 273–284.
[110]
Schlapschy, M.; Binder, U.; B？rger, C.; Theobald, I.; Wachinger, K.; Kisling, S.; Haller, D.; Skerra, A. PASylation: A biological alternative to PEGylation for extending the plasma half-life of pharmaceutically active proteins. Protein Eng. Des. Sel. 2013, 26, 489–501.
