Designing PEGylated therapeutic molecules: Advantages in ADMET properties

Expert Opinion on Drug Discovery

Volumn 3, Issue 11, 2008, Pages 1293-1307

  Hamidi, Mehrdad ^a,b   Rafiei, Pedram ^a   Azadi, Amir ^a  

^a SHIRAZ UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^b ZANJAN UNIVERSITY OF MEDICAL SCIENCES   (Iran)

Author keywords

Molecular conjugation; Particle conjugation; PEG; PEGylation

Indexed keywords

ADENOSINE DEAMINASE; ALPHA INTERFERON; APTAMER; APTANIB; ASPARAGINASE; ASPARAGINASE MACROGOL; CALCITONIN; CAMPTOTHECIN; CERTOLIZUMAB PEGOL; CISPLATIN; COPOLYMER; DOXORUBICIN; GLUCAGON LIKE PEPTIDE 1; GRANULOCYTE COLONY STIMULATING FACTOR; INTRALIPID; LIPOSOME; MACROGOL; OLIGONUCLEOTIDE; OVALBUMIN; PACLITAXEL; PEGADEMASE; PEGAPTANIB; PEGINTERFERON ALPHA2A; PEGINTERFERON ALPHA2B; PEGVISOMANT; RECOMBINANT ALPHA2B INTERFERON; RECOMBINANT GRANULOCYTE COLONY STIMULATING FACTOR; SUPEROXIDE DISMUTASE; TRANSFERRIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; URATE OXIDASE;

CLINICAL TRIAL; DRUG BIOAVAILABILITY; DRUG CONJUGATION; DRUG DELIVERY SYSTEM; DRUG DESIGN; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG FORMULATION; DRUG STRUCTURE; HUMAN; IMMUNOGENICITY; KIDNEY CLEARANCE; MOLECULAR WEIGHT; NONHUMAN; PARTICULATE MATTER; PLASMA HALF LIFE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DEPLETION; REVIEW; SHELF LIFE; TISSUE DISTRIBUTION;

EID: 56749098212     PISSN: 17460441     EISSN: None     Source Type: Journal    
DOI: 10.1517/17460441.3.11.1293     Document Type: Review

References (97)

1. Davis FF, Abuchowski A, Van Es T, et al. Enzyme-polyethylene glycol adducts: modified enzymes with unique properties. Enzyme Eng 1978;4:169-73
2. Harris JM, Martin NE, Modi M. Pegylation: a novel process for modifying pharmacokinetics. Clin Pharmacokinet 2001;40:539-51
3. Harris JM, Chess RB. Effect of pegylation on pharmaceuticals. Nat Rev Drug Discov 2003;2:214-21
4. Reddy KR. Controlled-release, pegylation, liposomal formulations: new mechanisms in the delivery of injectable drugs. Ann Pharmacother 2000;34:915-23
5. Fishburn CS. The Pharmacology of PEGylation: Balancing PD with PK to Generate Novel Therapeutics. J Pharm Sci 2008: published online 15 Jan 2008, DOI: 10.1002/jps.21278
6. Veronese FM, Pasut G. PEGylation, successful approach to drug delivery. Drug Discov Today 2005;10:1451-8
7. Pasut G, et al. Protein, peptide and nonpeptide drug PEGylation for therapeutic application: a review. Exp Opin Ther Patents 2004;14:859-94
8. Caliceti P, Veronese FM. Pharmacokinetic and biodistribution properties of poly(ethylene glycol)-protein conjugates. Adv Drug Deliv Rev 2003;55:1261-77
9. Fontana A, Spolaore B, Mero A, Veronese FM. Site-specific modification and PEGylation of pharmaceutical proteins mediated by transglutaminase. Adv Drug Deliv Rev 2008;60:13-28
10. Zalipsky S. Chemistry of polyethylene glycol conjugates with biologically active molecules. Adv Drug Deliv Rev 1995;16:157-82
11. Sato H. Enzymatic procedure for sitespecific pegylation of proteins. Adv Drug Deliv Rev 2002;54:487-504
12. De Frees S, et al. Glycopegylation methods and proteins/peptides produced by the methods. Neose Technologies WO2004099231 2004;
13. Chen T, et al. Nature-inspired creation of protein-polysaccharide conjugate and its subsequent assembly onto a patterned surface. Langmuir 2003;19:9382-86
14. Choe YH, et al. Anticancer drug delivery systems: multi-loaded N4-acyl poly(ethyleneglycol) prodrugs of ara-C.: II. Efficacy in ascites and solid tumors. J Control Rel 2002;79:55-70
15. Wattendorf U, Merkle HP. PEGylation as a Tool for the Biomedical Engineering of Surface Modified Microparticles. J Pharm Sci 2008: published online 27 Feb 2008, DOI: 10.1002/jps.21350
16. Otsuka H, Nagasaki Y, Kataoka K. PEGylated nanoparticles for biological and pharmaceutical applications. Adv Drug Deliv Rev 2003;55:403-19
17. Diwan M, Park TG. Pegylation enhances protein stability during encapsulation in PLGA microspheres. J Control Rel 2001;73:233-44
18. Parveen S, Sahoo SK. Nanomedicine: clinical applications of polyethylene glycol conjugated proteins and drugs. Clin Pharmacokinet 2006;45:965-88
19. Gaberc-Porekar V, Zore I, Podobnik B, et al. Obstacles and pitfalls in the PEGylation of therapeutic proteins. Curr Opin Drug Discov Devel 2008;11:242-50
20. Pasut G, et al. Protein, peptide and nonpeptide drug PEGylation for therapeutic application: a review. Exp Op Ther Patents 2004;14:859-94
21. Parrish B, Emrick T. Soluble camptothecin derivatives prepared by click cycloaddition chemistry on functional aliphatic polyesters. Bioconjug Chem 2007;18:263-7
22. Haverstick K, Fleming A, Mark Saltzman W. Conjugation to increase treatment volume during local therapy: a case study with PEGylated camptothecin. Bioconjug Chem 2007;18:2115-21
23. Anabousi S, Kleemann E, Bakowsky U, et al. Effect of PEGylation on the stability of liposomes during nebulisation and in lung surfactant. J Nanosci Nanotechnol 2006;6:3010-6
24. Otsuka H, Nagasaki Y, Kataoka K. PEGylated nanoparticles for biological and pharmaceutical applications. Adv Drug Deliv Rev 2003;55:403-19
25. Craparo EF, Cavallaro G, Bondi ML, et al. PEGylated Nanoparticles based on a polyaspartamide, preparation, physico-chemical characterization, and intracellular uptake. Biomacromolecules 2006;7:3083-92
26. Zhang Y, Chen J, Zhang Y, et al. A novel PEGylation of chitosan nanoparticles for gene delivery. Biotechnol Appl Biochem 2007;46:197-204
27. Suh J, Choy KL, Lai SK, et al. PEGylation of nanoparticles improves their cytoplasmic transport. Int J Nanomedicine 2007;2:735-41
28. Chirila TV, Rakoczy PE, Garrett KL, et al. The use of synthetic polymers for delivery of therapeutic antisense oligodeoxynucleotides. Biomaterials 2002;23:321-32
29. Remaut K, Lucas B, Raemdonck K, et al. Protection of oligonucleotides against enzymatic degradation by pegylated and nonpegylated branched polyethyleneimine. Biomacromolecules 2007;8:1333-40
30. The EyeTech Study Group Preclinical and phase 1A clinical evaluation of an anti-VEGF pegylated aptamer (EYE001) for the treatment of exudative age-related macular degeneration. Retina 2002;22:143-52
31. Monfardini C, Veronese FM. Stabilization of substances in circulation, Bioconjug Chem 1998;9:418-50
32. Fuertges F, Abuchowski A. The clinical efficacy of poly(ethylene glycol)-modified proteins. J Control Release 1990;11:139-48
33. Veronese FM, Caliceti P, Pastorino A, et al. Preparation, physicochemical and pharmacokinctic characterization of monomethoxypoly(ethylene glycol)-derivatized superoxide dismutase. J Control Release 1989;10:145-54
34. Youn YS, Jeon JE, Chae SY, et al. PEGylation improves the hypoglycaemic efficacy of intranasally administered glucagon-like peptide-1 in type 2 diabetic db/db mice.: Diabetes Obes Metab 2008;10:343-6
35. Veronese FM. Peptide and protein PEGylation: a review of problems and solutions. Biomaterials 2001;22:405-17
36. Takakura Y, Fujita T, Hashida M, Sezaki H. Disposition of macromolecules in tumor bearing mice. Pharm Res 1990;7:339-46
37. Friman S, Egestad B, Sjövall J, Svanvik J. Hepatic excretion and metabolism of polyethylene glycols and mannitol in the cat. J Hepatol 1993;17:48-55
38. Beranová M, Wasserbauer R, Vanèurová D, et al. Effect of cyrochrome P-450 inhibition and stimulation on intensity of polyethylene degradation in microsomal fraction of mouse and rat livers. Biomaterials 1990;11(7):521-4
39. Mehvar R. Modulation of the pharmacokineiics and pharmacodynamics of proteins by polyethylene glycol conjugation. J Pharm Pharm Sci 2003;3(1):125-36
40. Herold DA, Keil K, Bruns DE. Oxidation of polyethyleneglycols by alcohol dehydrogenase. Biochem Pharmacol 1989;38(1):73-6
41. Seongok H, Chongyoup K, Kwon D. Thermal/oxidative degradation and stabilization of polyethylene glycol. Polymer 1997;38:317-23
42. Modi MW, Fulton JS, Buchmann DK, et al. Clearance of PEGylated (40 kDa) interferon alfa-2a(Pegasys®) is primarily hepatic. Hepatol 2000; 32:371A
43. Cheng TL, Wu PY, Wu MF, et al. Accelerated clearance of polyethylene glycol-modified proteins by anti-polyethylene glycol IgM. Bioconjug Chem 1999;10:520-8
44. Cheng TL, Cheng BM, Chern JW, et al. Efficient clearance of poly(ethylene glycol)-modified immunoenzyme with anti-PEG monoclonal antibody for prodrug cancer therapy. Bioconjug Chem 2000;11:258-66
45. Richter AW, Akerblom E. Antibodies against polyethyleneglycol produced in animals by immunization with monomethoxy polyethylene glycol modified proteins. Int Arch Allergy Appl Immunol 1983;70:124-31
46. Noguchi Y, Wan J, Duncan R, et al. Early phase tumor accumulation of macromolecules: a great difference in clearance rate between tumor and normal tissues. Jpn J Cancer 1998;89:397-416
47. Murakami Y, Tabata Y, Ikada Y. Tumor accumulation of poly(ethylene glycol) with different molecular weights after i.v. injection. Drug Del 1997;4:23-32
48. Gabizon A, Chemla M, Tzemach D, et al. Liposome longevity and stability in circulation: effects on the in vivo delivery to tumors and therapeutic efficacy of encapsulated anthracyclines. J Drug Target 1996;3:391-8
49. Alberts DS, Garcia DJ. Safety aspects of pegylated liposomal doxorubicin in patients with cancer. Drugs 1997;54:30-5
50. Gabizon A, Martin F. Polyethylene glycol-coated liposomal doxorubicin: rationale for use in solid tumors. Drugs 1997;54:15-21
51. Sharp M, Easthope SE, Keating GM, Lamb HM. Polyethylene glycol-liposomal doxorubicin. Drugs 2002;62:2089-126
52. Illum L, Church AE, Butterworth MD, et al. Development of systems for targeting the regional lymph nodes for diagnostic imaging. Pharm Res 2001;18:640-5
53. Ishida O, Maruyama K, Tanahashi H, et al. Liposomes bearing polyethyleneglycol-coupled transferrin with intracellular targeting property to the solid tumors. Pharm Res 2001;18:1042-8
54. Conover CD, Greenwald RB, Pendri A, et al. Camptothecin delivery systems: enhanced efficacy and tumor accumulation of camptothecin following its conjugation to polyethylene glycol via a glycine linker. Cancer Chemother Pharmacol 1998;42:407-14
55. Wills RJ, Dennis S, Speigel HE, et al. Interferon kinetics and adverse reactions after intravenous, intramuscular, and subcutaneous injection. Clin Pharmacol Ther 1984;35:722-7
56. Algranati NE, Sy S, Modi M. A branched methoxy 40 kDa poly ethylene glycol (PEG) moiety optimizes the pharmacokinetics (PK) of PEGinterferon α 2a (PEG-IFN) and may explain its enhanced efficacy in chronic hepatitis C (CHC). Hepatology 1999;40(suppl):190A
57. Chatelur E, Rostaing L, Gregoire N, et al. A pharmacokinetic model for alpha interferon administered subcutaneously. Br J Clin Pharmacol 1999;47:365-71
58. Xu ZX, Patel I, Joubert P. Single-dose safety/tolerability and pharmacokinetic/pharmacodynamics (PK/PD) following administration of ascending subcutaneous doses of pegylated interferon (PEG-IFN) and interferon α-2a (IFN α-2a) to healthy subjects. Hepatology 1998;28(Suppl):702
59. Pardridge WM, Wu D, Sakane T. Combined use of carboxyl directed protein pegylation and vector-mediated blood-brain barrier drug delivery system optimized brain uptake of brain derived neurotrophic factor following intravenous administration. Pharm Res 1998;15:576-82
60. Knauf MJ, Bell DP, Hirtzer P, et al. Relationship of effective molecular size to systemic clearance in rats of recombinant interleukin-2 chemically modified with water-soluble polymers. J Biol Chem 1988;263:15064-70
61. Holle LM. Pegaspargase: alternative? Ann Pharmacother 1997;31:616-24, 655-6
62. Brenner B, Rector JF. Brenner and Rector's: the Kidney, 5th edition. Philadelphia: W.B. Saunders Company, 1996
63. Burnham NL. Polymers for delivering peptides and proteins. Am Jb Hosp Pharm 1994;51:210-8
64. Bailon P, Spence C, Schaffer CA, et al. Pharmacological properties of five polyethylene glycol conjugates of interferon-α-2a. International Conference on Therapies for Viral Hepatitis; 1999 Dec 6, Maui, Hawaii
65. Yamaoka T, Tabata Y, Ikada Y. Distribution and tissue uptake of poly(ethylene glycol) with different molecular weights after intravenous administration to mice. J Pharm Sci 1994;83:601-6
66. Jaschke A, Furste JP, Nordhoff E, et al. Synthesis and properties of oligodeoxyribonucleotide-polyethylene glycol conjugates. Nuleic Acids Res 1994;22:4810-7
67. Seelig B, Jasche A. Site specific modification of enzymatically synthesized RNA: transcription initiation and Diels Alder reaction. Tetrahedran Lett 1997;38:7729-32
68. Nieforth KA, Nadeau R, Patel IH, et al. Use of an indirect pharmacodynamic stimulation model of MX protein induction to compare in vivo activity of interferon alfa-2a and a polyethylene glycol-modified derivative in healthy subjects. Clin Pharmacol Ther 1996;59:636-46
69. Glue P, Rouzier-panis R, Raffanel C, et al. PEG-interferon-α 2b: pharmacokinetics, pharmacodynamics, safety and preliminary efficacy data. Hepatology 1999;30:189AA
70. Bukowski RM, Tendler C, Cutler D, et al. Treating cancer with PEG Intron: pharmacokinetic profile and dosing guidelines for an improved interferon-alpha-2b formulation. Cancer 2002;95:389-96
71. Fujita T, Nishikawa M, Ohtsubo Y, et al. Control of in vivo fate of albumin derivatives utilizing combined chemical modification. J Drug Target 1994;2:157-65
72. Hershfield MS. Biochemistry and poly (ethylene glycol)-modified adenosine deaminase (PEG-ADA). In: Harris JM, Zolipsky S. Poly (ethylene glycol): Chemistry and Biological Applications, editors, Washington DC: ACS Books, 1997
73. Koumenis IL, Shahrokh Z, Leong S, et al. Modulating pharmacokinetics of an anti-interieukin-8 F(ab′)2 by amine specific PEGylation with preserved bioactivity. Int J Pharm 2000;198:83-95
74. Esslinger HV, Haas S, Maurer R, et al. Pharmacodynamic and safety results of PEG-Hirudin in healthy volunteers. Thromb Haemost 1997;77:911-19
75. Tsutsumi Y, Tsunoda S, Kamada H, et al. PEGylation of interleukin-6 effectively increases its thrombopoietic potency. Thromb Haemost 1997;77:168-73
76. Tsutsumi Y, Kihira T, Tsunoda S, et al. Molecular design of hybrid tumour necrosis factor alfa with polyethylene glycol increases its anti-tumour potency. Br J Cancer 1995;71:963-8
77. Hokom MM, Lacey D, Kinsler O, et al. Pegylated megakaryocyte growth and development factor abrogates the lethal thrombocytopenia associated with carboplatin and irradiation in mice. Blood 1995;86:4486-92
78. Beauchamp CO, Gonias SL, Menapace DP, et al. A new procedure for the synthesis of polyethylene glycol-protein adducts; effects on function, receptor recognition, and clearance of superoxide dismutase, lactoferrin, and alfa 2-macroglobulin. Anal Biochem 1983;131:25-33
79. Rajagopalan S, Gonias SL, Pizzo SV. A nonantigenic covalent streptokinase-polyethylene glycol complex with plasminogen activator function. J Clin Invest 1985;75:413-9
80. Bazile DV, Ropert C, Huve PV, et al. Body distribution of fully biodegradable [14C]-poly(lactic acid) nanoparticles coated with albumin after parenteral administration to rats. Biomaterials 1992;13:1093-102
81. Stolnik S, Dunn SE, Garnett MC, et al. Surface modification of poly(lactide-co-glycolide) nanospheres by biodegradable poly(lactide)-poly(ethylene glycol) copolymers. Pharm Res 1994;11:1800-8
82. Verrecchia T, Spenlehauer G, Bazile DV, et al. Non-stealth (poly(lactic acid/albumin)) and stealth (poly(lactic acid-polyethylene glycol)) nanoparticles as injectable drug carriers. J Control Rel 1995;36:49-61
83. Li Y, Pei Y, Zhang X, et al. PEGylated PLGA nanoparticles as protein carriers: synthesis, preparation and biodistribution in rats. J Control Rel 2001;71:203-11
84. Allemann E, Gravel P, Leroux JC, et al. Kinetics of blood component adsorption on poly(D,L-lactic acid) nanoparticles: evidence of complement C3 component involvement. J Biomed Mater Res 1997;37:229-34
85. Moghimi SM, Hunter, AC, Murray JC. Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol Rev 2001;53:283-318
86. Riley T, Govender T, Stolnik S, et al. Colloidal stability and drug incorporation aspects of micellar-like PLA-PEG nanoparticles. Colloids Surf B Biointerfaces 1999;16:147-59
87. Chognot D, Six JL, Leonard M, et al. Physicochemical evaluation of PLA nanoparticles stabilized by water-soluble MPEO-PLA block copolymers. J Colloid Interface Sci 2003;268:441-7
88. Gref R, Lück M, Quellec P, et al. 'Stealth' corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. Colloids Surf B Biointerfaces 2000;18:301-13
89. Sahli H, Tapon-Bretaudiere J, Fischer AM, et al. Interactions of poly(lactic acid) and poly(lactic acid-co-ethylene oxide) nanoparticles with the plasma factors of the coagulation system. Biomaterials 1997;18:281-8
90. Bazile D, Prud'homme C, Bassoullet MT, et al. Stealth Me.PEGPLA nanoparticles avoid uptake by the mononuclear phagocytes system. J Pharm Sci 1995;84:493-8
91. Zambaux MF, Faivre-Fiorina B, Bonneau F, et al. Involvement of neutrophilic granulocytes in the uptake of biodegradable non-stealth and stealth nanoparticles in guinea pig. Biomaterials 2000;21:975-80
92. Gref R, Domb A, Quellec P, et al. The controlled intravenous delivery bof drugs using PEG-coated sterically stabilized nanospheres. Adv Drug Deliv Rev 1995;16:215-33
93. Mosqueira VC, Legrand P, Gulik A, et al. Relationship between complement activation, cellular uptake and surface physicochemical aspects of novel PEG-modified nanocapsules. Biomaterials 2001;22:2967-79
94. Gref R, Minamitake Y, Peracchia MT, et al. Biodegradable longcirculating polymeric nanospheres. Science 1994;263:1600-3
95. Novakova K, Laznicek M, Rypacek F, Machova L. Pharmacokinetics and distribution 125 I-PLA-b-PEO block copolymers in rats. Pharm Dev Technol 2003;8:153-61
96. Gbadamosi JK, Hunter AC, Moghimi SM. PEGylation of microspheres generates a heterogeneous population of particles with differential surface characteristics and biological performance. FEBS Lett 2002;532:338-44
97. Moghimi SM. Chemical camouflage of nanospheres with a poorly reactive surface: towards development of stealth and target-specific nanocarriers. Biochim Biophys Acta 2002;1590:131-9