8,466
Views
124
CrossRef citations to date
0
Altmetric
Focus on Nanotoxicology

Toxicity and immunogenicity concerns related to PEGylated-micelle carrier systems: a review

&
Pages 324-336 | Received 20 Nov 2018, Accepted 01 Mar 2019, Published online: 15 Apr 2019

References

  • Bader H, Ringsdorf H. Water soluble polymers in medicine. Angew Makromol Chem. 1984;123/124:457–485.
  • Yokoyama M. Polymeric micelle drug carriers for tumor targeting. In: Chapter 3, Svenson S, editor. Polymeric drug delivery I: particulate drug carriers. Washington: Oxford University Press; 2006. p. 27–39.
  • Yokoyama M. Polymeric micelles as a new drug carrier system and their required considerations for clinical trials. Expert Opin Drug Deliv. 2010;7:145–158.
  • Gabizon A, Isacson R, Rosengarten O, et al. An open-label study to evaluate dose and cycle dependence of the pharmacokinetics of pegylated liposomal doxorubicin. Cancer Chemother Pharmacol. 2008;61:695–702.
  • Kawaguchi T, Yamamoto T, Yokoyama M, et al. Histological study on side effects and tumor targeting of a block copolymer micelle on rats. J Control Release. 2009;136:240–246.
  • Yamamoto T, Yokoyama M, Opanasopit P, et al. What are determining factors for stable drug incorporation into polymeric micelle carriers? Consideration on physical and chemical characters of the micelle inner core. J Control Release. 2007;23:11–18.
  • Kawano K, Watanabe M, Yamamoto T, et al. Enhanced antitumor effect of camptothecin loaded in long-circulating polymeric micelles. J Control Release. 2006;112:329–:332.
  • Chansri N, Kawakami S, Yokoyama M, et al. Anti-tumor effect of all-trans retinoic acid loaded polymeric micelles in solid tumor bearing mice. Pharm Res. 2008;25:428–434.
  • Satoh T, Higuchi Y, Kawakami S, et al. Encapsulation of the synthetic retinoids Am80 and LE540 into polymeric micelles and the retinoids’ release control. J Control Release. 2009;136:187–195.
  • Ivens IA, Achanzar W, Baumann A, et al. PEGylated biopharmaceuticals: current experience and considerations for nonclinical development. Toxicol Pathol. 2015;3:959–983.
  • Turecek PL, Bossard MJ, Schoetens F, et al. PEGylation of biopharmaceuticals: a review of chemistry and nonclinical safety information of approved drugs. J Pharm Sci. 2016;105:460–475.
  • Knop K, Hoogenboom R, Fischer D, et al. Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives. Angew Chem Int Ed. 2010;49:6288–6308.
  • Kang JS, DeLuca PP, Lee KC. Emerging PEGylated drugs. Expert Opin Emerging Drugs. 2009;14:363–380.
  • Shiraishi K, Sanada Y, Mochizuki S, et al. Determination of polymeric micelles’ structural characteristics, and effect of the characteristics on pharmacokinetic behaviors. J Control Release. 2015;203:77–84.
  • Yang Q, Jones SW, Parker CL, et al. Evading immune cell uptake and clearance requires PEG grafting at densities substantially exceeding the minimum for brush conformation. Mol Pharm. 2014;11:1250–1258.
  • Walkey CD, Olsen JB, Guo H, et al. Nanoparticle size and surface chemistry determine serum protein adsorption and macrophage uptake. J Am Chem Soc. 2012;134:2139–2147.
  • Perry JL, Reuter KG, Kai MP, et al. Nano Lett. PEGylated PRINT nanoparticles: the impact of PEG density on protein binding, macrophage association, biodistribution, and pharmacokinetics. Nano Lett. 2012;12:5304–5310.
  • Sanada Y, Akiba I, Hashida S, et al. Composition dependence of the micellar architecture made from poly(ethylene glycol)-block-poly(partially benzyl-esterified aspartic acid). J Phys Chem B. 2012;116:8241–8250.
  • Abuchowski A, Es TV, Palczuk NC, et al. Alteration of immunological properties of bovine serum albumin by covalent attachment of polyethylene glycol. J Biol Chem. 1977;252:3578–3581.
  • Klibanov AL, Maruyama K, Torchilin VP, et al. Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett. 1990;268:235–237.
  • Barenholz YC. Doxil®—the first FDA-approved nano-drug: lessons learned. J Control Release. 2012;160:117–134.
  • Lipsky PE, Calabrese LH, Kavanaugh A, et al. Pegloticase immunogenicity: the relationship between efficacy and antibody development in patients treated for refractory chronic gout. Arthritis Res Ther. 2014;16:R60.
  • Armstrong JK, Hempel G, Koling S, et al. Antibody against poly(ethylene glycol) adversely affects peg-asparaginase therapy in acute lymphoblastic leukemia patients. Cancer. 2007;10:103–111.
  • Ganson NJ, Kelly SJ, Scarlett E, et al. 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. 2006;8:R12.
  • Longo N, Harding CO, Burton BK, et al. Single-dose, subcutaneous recombinant phenylalanine ammonia lyase conjugated with polyethylene glycol in adult patients with phenylketonuria: an open-label, multicentre, phase 1 dose-escalation trial. Lancet. 2014;384:37–44.
  • Hershfield MS, Ganson NJ, Kelly SJ, et al. Induced and pre-existing anti-polyethylene glycol antibody in a trial of every 3-week dosing of pegloticase for refractory gout, including in organ transplant recipients. Arthritis Res Ther. 2014;16:R63.
  • Garay RP, El-Gewely R, Armstrong JK, et al. Antibodies against polyethylene glycol in healthy subjects and in patients treated with PEG-conjugated agents. Expert Opin Drug Deliv. 2012;9:1319–1323.
  • Ganson NJ, Povsic TJ, Sullenger BA, et al. Pre-existing anti-PEG antibody linked to first-exposure allergic reactions to pegnivacogin, a PEGylated RNA aptamer. J Allergy Clin Immunol. 2016;137:1610–1613.
  • Moghimi SM, Gray T. A single dose of intravenously injected poloxamine-coated long-circulating particles triggers macrophage clearance of subsequent doses in rats. Clin Sci. 1997;93:371–379.
  • Dams ETM, Laverman P, Oyen WJG, et al. Accelerated blood clearance and altered biodistribution of repeated injections of sterically stabilized liposomes. J Pharm Exp Ther. 2000;292:1071–1079.
  • Laverman P, Carstens MG, Boerman OC, et al. Factors affecting the accelerated blood clearance of polyethylene glycol-liposomes upon repeated injection. J Pharm Exp Ther. 2001;298:607–612.
  • Shiraishi K, Kawano K, Minowa T, et al. Preparation and in vivo imaging of PEG-poly(L-lysine)-based polymeric micelle MRI contrast agents. J Control Release. 2009;136:14–20.
  • Schellekens H, Hennink WE, Brinks V. The immunogenicity of polyethylene glycol: facts and fiction. Pharm Res. 2013;30:1729–1734.
  • Yang Q, Lai SK. Anti-PEG immunity: emergence, characteristics, and unaddressed questions. Nanomed Nanobiotechnol. 2015;7:655–677.
  • Lubich C, Allacher P, de la Rosa M, et al. The mystery of antibodies against polyethylene glycol (PEG): what do we know? Pharm Res. 2016;33:2239–2249.
  • Zhang P, Sun F, Liu S, et al. Anti-PEG antibodies in the clinic: current issues and beyond PEGylation. J Control Release. 2016;244:184–193.
  • Ishida T, Ichiahara M, Wang XY, et al. Injection of PEGylated liposomes in rats elicits PEG-specific IgM, which is responsible for rapid elimination of a second dose of PEGylated liposomes. J Control Release. 2006;112:15–25.
  • Verhoef JJF, Carpenter JF, Anchordoquy TJ, et al. Potential induction of anti-PEG antibodies and complement activation toward PEGylated therapeutics. Drug Discov Today. 2014;19:1945–1952.
  • Moghimi SM, Anderson AJ, Ahmadvand A, et al. Material properties in complement activation. Adv Drug Deliv Rev. 2011;63:1000–1007.
  • Moghimi SM, Hamad I, Andersen TL, et al. Methylation of the phosphate oxygen moiety of phospholipid-methoxy(polyethylene glycol) conjugate prevents PEGylated liposome-mediated complement activation and anaphylatoxin production. FASEB J. 2006;20:2591–2593.
  • Abbas AK, Lichtman AH. Basic immunology: functions and disorders of the immune system. Cambridge (MA): Elsevier; 2006.
  • Cheng X, Wang C, Su Y, et al. Enhanced opsonization-independent phagocytosis and high response ability to opsonized antigen–antibody complexes: a new role of kupffer cells in the accelerated blood clearance phenomenon upon repeated injection of PEGylated emulsions. Mol Pharm. 2018;15:3755–3766.
  • Moghimi SM. Cancer nanomedicine and the complement system activation paradigm: anaphylaxis and tumour growth. J Control Release. 2014;190:556–562.
  • La-Beck NM, Gabizon AA. Nanoparticle interactions with the immune system: clinical implications for Liposome-Based cancer chemotherapy. Front Immunol. 2017;8:00416.
  • Ma H, Shiraishi K, Minowa T, et al. Accelerated blood clearance was not induced for a gadolinium-containing PEG-poly(L-lysine)-based polymeric micelle in mice. Pharm Res. 2010;27:296–302.
  • Romberg B, Oussoren C, Snel CJ, et al. Pharmacokinetics of poly(hydroxyethyl-L-asparagine)-coated liposomes is superior over that of PEG-coated liposomes at low lipid dose and upon repeated administration. Biochim Biophys Acta. 2007;768:737–743.
  • Lila ASA, Nawata K, Shimizu T, et al. Use of polyglycerol (PG), instead of polyethylene glycol (PEG), prevents induction of the accelerated blood clearance phenomenon against long-circulating liposomes upon repeated administration. Int J Pharm. 2013;456:235–242.
  • Ishihara T, Maeda T, Sakamoto H, et al. Evasion of the accelerated blood clearance phenomenon by coating of nanoparticles with various hydrophilic polymers. Biomacromolecules. 2010;11:2700–2706.
  • Shiraishi K, Hamano M, Ma H, et al. Hydrophobic blocks of PEG-conjugates play a significant role in the accelerated blood clearance (ABC) phenomenon. J Control Release. 2013;165:183–190.
  • Ishida T, Atobe K, Wang XY, et al. Accelerated blood clearance of PEGylated liposomes upon repeated injections: effect of doxorubicin-encapsulation and high-dose first injection. J Control Release. 2006;115:251–258.
  • Chanan-Khan A, Szebeni J, Savay S, et al. Complement activation following first exposure to pegylated liposomal doxorubicin (Doxil®): possible role in hypersensitivity reactions. Annal Oncol. 2003;14:1430–1437.
  • Neun BW, Barenholz Y, Szebeni J, et al. Understanding the role of anti-PEG antibodies in the complement activation by Doxil in vitro. Molecules. 2018;23:1700–1718.
  • Richter AW, Åkerblom E. Antibodies against polyethylene glycol produced in animals by immunization with monomethoxy polyethylene glycol modified proteins. Int Archs Allergy Appl Immun. 1983;70:124–131.
  • Shiraishi K, Kawano K, Maitani Y, et al. Exploring the relationship between anti-PEG IgM behaviors and PEGylated nanoparticles and its significance for accelerated blood clearance. J Control Release. 2016;234:59–67.
  • Ishida T, Ichihara M, Wang XY, et al. Spleen plays an important role in the induction of accelerated blood clearance of PEGylated liposomes. J Control Release. 2006;115:243–250.
  • Shimizu T, Ishida T, Kiwada H. Transport of PEGylated liposomes from the splenic marginal zone to the follicle in the induction phase of the accelerated blood clearance phenomenon. Immunobiology. 2015;220:1151–1160.
  • Ishida T, Wang XY, Shimizu T, et al. PEGylated liposomes elicit an anti-PEG IgM response in a T cell-independent manner. J Control Release. 2007;122:349–355.
  • Koide H, Asai T, Hatanaka K, et al. T cell-independent B cell response is responsible for ABC phenomenon induced by repeated injection of PEGylated liposomes. Int J Pharm. 2010;392:218–2223.
  • Ichihara M, Shimizu T, Imoto A, et al. Anti-PEG IgM response against PEGylated liposomes in mice and rats. Pharmaceutics. 2011;3:1–11.
  • Moghimi SM, Anderson AJ, Hashemi SH, et al. Complement activation cascade triggered by PEG–PL engineered nanomedicines and carbon nanotubes: the challenges ahead. J Control Release. 2010;146:175–181.
  • Hamad I, Hunter AC, Moghimi SM. Complement monitoring of Pluronic 127 gel and micelles: suppression of copolymer-mediated complement activation by elevated serum levels of HDL, LDL, and apolipoproteins AI and B-100. J Control Release. 2013;170:167–174.
  • Devine DV, Wong K, Serrano K, et al. Liposome-complement interactions in rat serum: implications for liposome survival studies. Biochim Biophys Acta. 1994;1191:43–51.
  • Anderson AJ, Robinson JT, Dai H, et al. Single-walled carbon nanotube surface control of complement recognition and activation. ACS Nano. 2013;7:1108–1119.
  • Moghimi SM, Simberg D. Complement activation turnover on surfaces of nanoparticles. Nano Today. 2017;15:8–10.
  • Chen F, Wang G, Griffin JI, et al. Complement proteins bind to nanoparticle protein corona and undergo dynamic exchange in vivo. Nat Nanotechnol. 2017;12:387–393.
  • Yu K, Lai BFL, Foley JH, et al. Modulation of complement activation and amplification on nanoparticle surfaces by glycopolymer conformation and chemistry. ACS Nano. 2014;8:7687–7703.
  • Hamad I, Al-Hanbali O, Hunter AC, et al. Distinct polymer architecture mediates switching of complement activation pathways at the nanosphere-serum interface: implications for stealth nanoparticle engineering. ACS Nano. 2010;4:6629–6638.
  • Ricklin D, Hajishengallis, Yang K, et al. Complement: a key system for immune surveillance and homeostasis. Nat Immunol. 2010;11:785–797.
  • Sherman MR, Williams LD, Sobczyk MA, et al. Role of the methoxy group in immune responses to mPEG-protein conjugates. Bioconj Chem. 2012;23:485–499.
  • Saifer MGP, Williams LD, Sobczyk MA, et al. Selectivity of binding of PEGs and PEG-like oligomers to anti-PEG antibodies induced by methoxyPEG-proteins. Mol Immunol. 2014;57:236–246.
  • Shimizu T, Lila ASA, Fujita R, et al. A hydroxyl PEG version of PEGylated liposomes and its impact on anti-PEG IgM induction and on the accelerated clearance of PEGylated liposomes. Eur J Pharm Biopharm. 2018;127:142–149.
  • Zhang P, Sun F, Hung H-C, et al. Sensitive and quantitative detection of anti-poly(ethylene glycol) (PEG) antibodies by methoxy-PEG-coated surface plasmon resonance sensors. Anal Chem. 2017;89:8217–8222.
  • Dong H, Mora JR, Brockus C, et al. Development of a generic anti-PEG antibody assay using BioScale’s acoustic membrane microparticle technology. AAPS J. 2015;17:1511–1516.
  • Shimizu T, Lila ASA, Awata M, et al. A cell assay for detecting anti-PEG immune response against PEG-modified therapeutics. Pharm Res. 2018;35:223.
  • Lin WW, Cheng YA, Kao CH, et al. Enhancement effect of a variable topology of a membrane-tethered anti-poly(ethylene glycol) antibody on the sensitivity for quantifying PEG and PEGylated molecules. Anal Chem. 2017;89:6082–6090.
  • Aćimović SS, Šipová-Jungová H, Emilsson G, et al. Antibody–antigen interaction dynamics revealed by analysis of single-molecule equilibrium fluctuations on individual plasmonic nanoparticle biosensors. ACS Nano. 2018;12:9958–9965.
  • Ishida T, Harada M, Wang XY. Accelerated blood clearance of PEGylated liposomes following preceding liposome injection: effects of lipid dose and PEG surface-density and chain length of the first-dose liposomes. J Control Release. 2005;105:305–317.
  • McCallen J, Prybylski J, Yang Q, et al. Cross-reactivity of select PEG-binding antibodies to other polymers containing a C-C-O backbone. ACS Biomater Sci Eng. 2017;3:1605–1615.
  • Ando H, Lila ASA, Kawanishi M, et al. Reactivity of IgM antibodies elicited by PEGylated liposomes or PEGylated lipoplex against auto and foreign antigens. J Control Release. 2018;270:114–119.
  • Zhang P, Sun F, Tsao C, et al. Zwitterionic gel encapsulation promotes protein stability, enhances pharmacokinetics, and reduces immunogenicity. Proc Nat Acad Sci. 2015;114:12046–12051.
  • Li B, Yuan Z, Zhang P, et al. Zwitterionic nanocages overcome the efficacy loss of biologic drugs. Adv Mater. 2018;30:1705728.
  • Zhang P, Jain P, Tsao C, et al. Polypeptides with high zwitterion density for safe and effective therapeutics. Angew Chem Int Ed. 2018;57:7743–7747.
  • Qi Y, Simakova A, Ganson NJ, et al. A brush-polymer/exendin-4 conjugate reduces blood glucose levels for up to five days and eliminates poly(ethylene glycol) antigenicity. Nat Biomed Eng. 2016;1:0002.
  • Qi Y, Chilkoti A. Protein-polymer conjugation – moving beyond PEGylation. Curr Opin Chem Biol. 2015;28:181–193.
  • Mima Y, Abu Lila AS, Shimizu T, et al. Ganglioside inserted into PEGylated liposome attenuates anti-PEG immunity. J Control Release. 2017;250:20–26.
  • Si Y, Liu M, Liang K, et al. Evaluating the accelerated blood clearance phenomenon of PEGylated nanoemulsions in rats by intraperitoneal administration. AAPS PharmSciTech. 2018;19:3210–3218.