653
Views
44
CrossRef citations to date
0
Altmetric
Journal of Drug Targeting Lifetime Achievement Award 2017

Polymer therapeutics at a crossroads? Finding the path for improved translation in the twenty-first century

Pages 759-780 | Received 17 Jul 2017, Accepted 17 Jul 2017, Published online: 08 Aug 2017

References

  • Bianconi E, Piovesan A, Facchin F, et al. An estimation of the number of cells in the human body. Ann Hum Biol. 2013;40:463–471.
  • Spalding KL. Retrospective birth dating of cells in humans. Cell. 2005;122:133–143.
  • McGuckin MA. Mucin dynamics and enteric pathogens. Nat Rev Microbiol. 2011;9:265–278.
  • Klarhöfer M, Csapo B, Balassy C, et al. High-resolution blood flow velocity measurements in the human finger. Magn Reson Med. 2001;45:716–719.
  • Guo C-L, Harris NC, Wijeratne SS, et al. Multiscale mechanobiology: mechanics at the molecular, cellular, and tissue levels. Cell Biosci. 2013;3:25.
  • Milo R. What is the total number of protein molecules per cell volume? A call to rethink some published values. Bioessays. 2013;35:1050–1055.
  • Ratner BD, Bryant SJ. Biomaterials: where we have been and where we are going. Annu Rev Biomed Eng. 2004;6:41–75.
  • Rowe RC, Sheskey PJ, Cook WG, et al., editors. Handbook of pharmaceutical excipients. 7th ed. London (UK): Pharmaceutical Press; 2012.
  • Heller J. Controlled release of biologically active compounds from bioerodible polymers. Biomaterials. 1980;1:51–57.
  • Duncan R. The dawning era of polymer therapeutics. Nat Rev Drug Discov. 2003;2:347–360.
  • Chiellini E, Giusti P, editors. Polymers in medicine: biomedical and pharmacological applications. New York: Plenum Press; 1983.
  • Duncan R, Kopecek J. Soluble synthetic polymers as potential drug carriers. Adv Polymer Sci. 1984;57:51–101.
  • Duncan R. Polymer therapeutics: top 10 selling pharmaceuticals: what next? J Control Release. 2014;190:371–380.
  • Duncan R, Vicent MJ. Polymer therapeutics-prospects for 21st century: the end of the beginning. Adv Drug Deliv Rev. 2013;65:60–70.
  • de Duve C, de Barsy T, Poole B, et al. Commentary. Lysosomotropic agents. Biochem Pharmacol. 1974;23:2495–2531.
  • de Duve C. The joy of discovery. Nature. 2010;467:S5.
  • Ringsdorf H. Structure and properties of pharmacologically active polymers. J Polym Sci C Polym Symp. 1975;51:135–153.
  • Newell DR, Searle KM, Westwood NB, et al. Professor Tom Connors and the development of novel cancer therapies by the phase I/II Clinical Trials Committee of Cancer Research UK. Br J Cancer. 2003;89:437–454.
  • Duncan R, Pratten MK. Membrane economics in endocytic systems. J Theor Biol. 1977;66:727–735.
  • Xu H, Ren D. Lysosomal physiology. Annu Rev Physiol. 2015;77:57–80.
  • Maxfield FR. Role of endosomes and lysosomes in human disease. Cold Spring Harb Perspect Biol. 2014;6:a016931.
  • Duncan R, Richardson SCW. Endocytosis and intracellular trafficking as gateways for nanomedicine delivery: opportunities and challenges. Mol Pharm. 2012;9:2380–2402.
  • Duncan R, Seymour LCW, Scarlett L, et al. Fate of N-(2-hydroxypropyl)methacrylamide copolymers with pendant galactosamine residues after intravenous administration to rats. Biochim Biophys Acta. 1986;880:62–71.
  • Huang Y. Preclinical and clinical advances of GalNAc-decorated nucleic acid therapeutics. Mol Ther Nucleic Acids. 2017;6:116–132.
  • Harris RL, van den Berg CW, Bowen DJ. ASGR1 and ASGR2, the genes that encode the asialoglycoprotein receptor (Ashwell Receptor), are expressed in peripheral blood monocytes and show interindividual differences in transcript profile. Mol Biol Int. 2012;2012:283974.
  • Vasey P, Kaye SB, Morrison R, et al. Phase I clinical and pharmacokinetic study of PK1 [N-(2-hydroxypropyl)methacrylamide copolymer doxorubicin]: first member of a new class of chemotherapeutic agents - drug-polymer conjugates. Clin Cancer Res. 1999;5:83–94.
  • Seymour LW, Ferry DR, Anderson D, et al. Hepatic drug targeting: phase I evaluation of polymer-bound doxorubicin. J Clin Oncol. 2002;20:1668–1676.
  • Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 1986;46:6387–6392.
  • Duncan R, Seymour LW, O'Hare KB, et al. Preclinical evaluation of polymer-bound doxorubicin. J Control Rel. 1992;19:331–346.
  • Duncan R. Development of HPMA copolymer-anticancer conjugates: clinical experience and lessons learnt. Adv Drug Deliv Rev. 2009;61:1131–1148.
  • Gianasi E, Wasil M, Evagorou EG, et al. HPMA copolymer platinates as novel antitumor agents: in-vitro properties, pharmacokinetics and antitumour activity in vivo. Eur J Cancer. 1999;35:994–1002.
  • Gianasi E, Buckley RG, Latigo J, et al. HPMA copolymer platinates containing dicarboxylato ligands. Preparation, characterisation and in vitro and in vivo evaluation. J Drug Target. 2002;10:549–556.
  • Hreczuk-Hirst D, Chicco D, German L, et al. Dextrins as potential carriers for drug targeting: tailored rates of dextrin degradation by introduction of pendant groups. Int J Pharm. 2001;230:57–66.
  • Hardwicke J, Ferguson EL, Moseley R, et al. Dextrin-rhEGF conjugates as bioresponsive nanomedicines for wound repair. J Control Release. 2008;130:275–283.
  • Duncan R, Gilbert HRP, Carbajo RJ, et al. Polymer masked-unmasked protein therapy (PUMPT). 1. Bioresponsive dextrin-trypsin and -MSH conjugates designed for α-amylase activation. Biomacromolecules. 2008;9:1146–1154.
  • Duncan R, Dimitrijevic S, Evagorou EG. The role of polymer conjugates in the diagnosis and treatment of cancer. STP Pharma Sci. 1996;6:237–263.
  • Davis FF. The origin of pegnology. Adv Drug Deliv Rev. 2002;54:457–458.
  • Beck B, Goetsch L, Dumontet C, et al. Strategies and challenges for the next generation of antibody-drug conjugates. Nat Rev Drug Discov. 2017;16:315–337.
  • Vella M, Pace D. Glycoconjugate vaccines: an update. Expert Opin Biol Ther. 2015;15:529–546.
  • Wakankar A, Chen Y, Gokarn Y, et al. Analytical methods for physicochemical characterization of antibody drug conjugates. MABS. 2011;3:161–172.
  • Gorovits B, Alley SC, Bilic S, et al. Bioanalysis of antibody–drug conjugates: American Association of Pharmaceutical Scientists Antibody–Drug Conjugate Working Group position paper. Bioanalysis. 2013;5:997–1006.
  • Charych DH, Hoch U, Langowski JL, et al. NKTR-214, an engineered cytokine with biased IL2 receptor binding, increased tumor exposure, and marked efficacy in mouse tumor models. Clin Cancer Res. 2016;22:680–690.
  • Hurwitz ME, Diab A, Bernatchez C, et al. Effect of NKTR-214 on the number and activity of CD8+ tumor infiltrating lymphocytes in patients with advanced renal cell carcinoma. J Clin Oncol. 2017;35(Suppl 6S):454.
  • Diab A, Tannir NM, Bernatchez C, et al. A phase 1/2 study of a novel IL-2 cytokine, NKTR-214, and nivolumab in patients with select locally advanced or metastatic solid tumors. J Clin Oncol. 2017;35(suppl):e14040.
  • Hingorani SR, Harris WP, Beck JT, et al. Phase Ib study of PEGylated recombinant human hyaluronidase and gemcitabine in patients with advanced pancreatic cancer. Clin Cancer Res. 2016;22:2848–2854.
  • Hingorani SR, Bullock AJ, Seery TE, et al. Randomized phase II study of PEGPH20 plus nab-paclitaxel/gemcitabine (PAG) vs AG in patients (Pts) with untreated, metastatic pancreatic ductal adenocarcinoma (mPDA). J Clin Oncol. 2017;35(Suppl):4008.
  • Mito JK, Ferrer JM, Brigman BE, et al. Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging. Cancer. 2002;118:5320–5330.
  • Whitley MJ, Cardona DM, Lazarides AL, et al. A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer. Sci Transl Med. 2016;8:320ra4.
  • Duncan R. Polymer therapeutics as nanomedicines: new perspectives. Curr Opin Biotechnol. 2011;22:1–10.
  • Burris HA, Barve MA, Hamilton EP, et al. A phase Ib, first-in-human, dose escalation and expansion study of XMT-1522, a novel antibody-drug conjugate (ADC) directed against HER2, in patients with advanced breast cancer and other advanced tumors expressing HER2. J Clin Oncol. 2017;35:TPS2606.
  • Lyman GH, Allcott K, Garcia J, et al. The effectiveness and safety of same-day versus next-day administration of long-acting granulocyte colony-stimulating factors for the prophylaxis of chemotherapy-induced neutropenia: a systematic review. Support Care Cancer. 2017;25:2619–2629.
  • Mahler LJ, DiBlasi R, Perez A, et al. On-body injector: an administration device for Pegfilgrastim. Clin J Oncol Nurs. 2017;21:121–122.
  • Muñoz-Garach A, Molina-Vega M, Tinahones FJ. How can a good idea fail? Basal insulin Peglispro [LY2605541] for the treatment of type 2 diabetes. Diabetes Ther. 2017;8:9–22.
  • Jolivalt CG, Rodriguez M, Wahren J, et al. Efficacy of a long-acting C-peptide analogue against peripheral neuropathy in streptozotocin-diabetic mice. Diabetes Obes Metab. 2015;17:781–788.
  • Li G, Zhao M, Zhao L. Well-defined hydroxyethyl starch-10-hydroxy camptothecin super macromolecule conjugate: cytotoxicity, pharmacodynamics research, tissue distribution test and intravenous injection safety assessment. Drug Deliv. 2016;23:2860–2868.
  • Wiedermann CJ, Eisendle K. Comparison of hydroxyethyl starch regulatory summaries from the Food and Drug Administration and the European Medicines Agency. J Pharm Policy Pract. 2017;21:12.
  • Hartog CS, Natanson C, Sun J, et al. Concerns over use of hydroxyethyl starch solutions. BMJ. 2014;349:g5981.
  • Cohen J, Belova A, Selmaj K, et al. Equivalence of generic glatiramer acetate in multiple sclerosis: a randomized clinical trial. JAMA Neurol. 2015;72:1433–1441.
  • Milani B, Gaspani S. Pathway to affordable, quality-assured sources of pegylated interferon alpha for treating hepatitis C. GaBI J. 2013;2:194–203.
  • Generics and Biosimilars Initiative. Biosimilars of pegfilgrastim. [Internet]. 2017. Available from: http://www.gabionline.net/Biosimilars/General/Biosimilars-of-pegfilgrastim
  • Hoggatt J, Tate TA, Pelus LM. Role of lipegfilgrastim in the management of chemotherapy-induced neutropenia. Int J Nanomed. 2015;10:2647–2652.
  • Weinstock-Guttman B, Nair KV, Glajch JL, et al. Two decades of glatiramer acetate: from initial discovery to the current development of generics. J Neurol Sci. 2017;376:255–259.
  • Arvedson T, O’Kelly J, Yang B-B. Design rationale and development approach for Pegfilgrastim as a long-acting granulocyte colony-stimulating factor. BioDrugs. 2015;29:185–198.
  • Wadhwa M, Bird C, Dougall T, et al. Establishment of the first international standard for PEGylated granulocyte colony stimulating factor (PEG-G-CSF): report of an international collaborative study. J Immunol Methods. 2015;416:17–28.
  • Israelachvili J. The different faces of poly(ethylene glycol). Proc Natl Acad Sci USA. 1997;94:8378–8379.
  • Zhang F, Liu M-R, Wan H-T. Discussion about several potential drawbacks of PEGylated therapeutic proteins. Biol Pharm Bull. 2014;37:335–339.
  • Schellekens H, Hennink WE, Brinks V. The immunogenicity of polyethylene glycol: facts and fiction. Pharm Res. 2013;30:1729–1734.
  • 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.
  • Yang Q, Jacobs TM, McCallen JD, et al. Analysis of pre-existing IgG and IgM antibodies against polyethylene glycol (PEG) in the general population. Anal Chem. 2016;88:11804–11812.
  • Ganson NJ, Povsic TJ, Sullenger BA, et al. Pre-existing anti-polyethylene glycol antibody linked to first-exposure allergic reactions to pegnivacogin, a PEGylated RNA aptamer. J Allergy Clin Immunol. 2016;137:1610–1613.
  • Maier KE, Levy M. From selection hits to clinical leads: progress in aptamer discovery. Mol Ther-Methods Clin Develop. 2016;5:16014.
  • Pratten MK, Duncan R, Lloyd JB. Adsorptive and passive pinocytic uptake. In: Ockleford CJ, Whyte A., editors. Coated vesicles. Cambridge: Cambridge University Press; 1980. p. 179–218.
  • Neufeld EF. Lysosomal storage diseases. Annu Rev Biochem. 1991;60:257–280.
  • Sultana N, Arayne S, Saify ZS. Polyvinylpyrolidone as plasma expander. JPMA. 1978;28:147–153.
  • Mohr W, Endres-Klein R. Do polyvinylpyrrolidone (PVP) deposits still occur in internal organs at the turn of the millennium? Observations on three patients from the former USSR. Pathologe. 2002;23:386–388.
  • Chi CC, Wang SH, Kuo TT. Localized cutaneous polyvinylpyrrolidone storage disease mimicking cheilitis granulomatosa. J Cutan Pathol. 2006;33:454–457.
  • 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.
  • Conover C, Lejeune L, Linberg R, et al. Transitional vacuole formation following a bolus infusion of PEG-hemoglobin in the rat. Artif Cells Blood Substit Immobil Biotechnol. 1996;24:599–611.
  • Bendele A, Seely J, Richey C, et al. Short communication: renal tubular vacuolation in animals treated with polyethylene-glycol-conjugated proteins. Toxicol Sci. 1998;42:152–157.
  • Ivens IA, Achanzar W, Baumann A, et al. PEGylated biopharmaceuticals: current experience and considerations for nonclinical development. Toxicol Pathol. 2015;43:959–983.
  • EMA/CHMP/SWP/647258/2012. CHMP Safety Working Party’s response to the PDCO regarding the use of PEGylated drug products in the paediatric population. 2012.
  • Ramos-Leví AM, Bernabeu I, Álvarez-Escolá C, et al. Long-term treatment with pegvisomant for acromegaly: a 10-year experience. Clin Endocrinol (Oxf). 2016;84:540–550.
  • Richardson SCW, Pattrick NG, Lavignac N, et al. Intracellular fate of bioresponsive poly(amidoamine)s in vitro and in vivo. J Control Release. 2010;142:78–88.
  • Duncan R, Pratten MK, Cable HC, et al. Effect of molecular size of 125I-labelled poly(vinylpyrrolidone) on its pinocytosis by rat visceral yolk sacs and rat peritoneal macrophages. Biochem J. 1980;196:49–55.
  • Clarke RM, Hardy RN. The use of [125-I]polyvinyl pyrrolidone K. 60 in the quantitative assessment of the uptake of macromolecular substances by the intestine of the young rat. J Physiol. 1969;204:113–125.
  • Cheng T-L, Chuang K-H, Chen B-M, et al. Analytical measurement of PEGylated molecules. Bioconjug Chem. 2012;23:881–899.
  • Lin WW, Hsieh Y-C, Cheng Y-A, et al. Optimization of an anti-poly(ethylene glycol) (anti-PEG) cell-based capture system to quantify PEG and PEGylated molecules. Anal Chem. 2016;88:12371–12379.
  • Gong J, Gu X, Achanzar WE, et al. Quantitative analysis of polyethylene glycol (PEG) and PEGylated proteins in animal tissues by LC-MS/MS coupled with in-source CID. Anal Chem. 2014;86:7642–7649.
  • Mahadevan U, Wolf DC, Dubinsky M, et al. Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2013;11:286–292.
  • Menjoge AR, Rinderknecht A, Navath RS, et al. Transfer of PAMAM dendrimers across human placenta: prospects of its use as drug carrier during pregnancy. J Control Rel. 2011;150:326–338.
  • Hassfurther RL, TerHune TN, Canning PC. Efficacy of polyethylene glycol-conjugated bovine granulocyte colony-stimulating factor for reducing the incidence of naturally occurring clinical mastitis in periparturient dairy cows and heifers. Am J Vet Res. 2015;76:231–238.
  • Duncan R, Gaspar R. Nanomedicine(s) under the microscope. Mol Pharm. 2011;8:2101–2141.
  • Rivera Gil P, Hühn D, del Mercato LL, et al. Nanopharmacy: inorganic nanoscale devices as vectors and active compounds. Pharmacol Res. 2010;62:115–125.
  • Venditto VJ, Szoka FC Jr. Cancer nanomedicines: so many papers and so few drugs! Adv Drug Deliv Rev. 2013;65:80–88.
  • Wilhelm S, Tavares AJ, Dai Q, et al. Analysis of nanoparticle delivery to tumours. Nat Rev Mater. 2016;1:1–12.
  • Phillips E, Penate-Medina O, Zanzonico PB, et al. Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe. Sci Transl Med. 2014;6:260ra149.
  • FDA. Guidance for Industry Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology. [Internet]; 2014. [cited 28 Jul 2017]. Available from: https://www.fda.gov/RegulatoryInformation/Guidances/ucm257698.htm
  • Ehmann F, Sakai-Kato K, Duncan R, et al. Next generation nanomedicines and nano-similars: EU Regulators’ initiatives relating to the development and evaluation of nanomedicines. Nanomedicine. 2013;8:849–856.
  • Ehmann F, Pita R. The EU is ready for non-biological complex medicinal products. GaBI J. 2016;5:30–35.
  • Tyner KM, Zheng N, Choi S, et al. How has CDER prepared for the nano revolution? A review of risk assessment, Regulatory research, and guidance activities. AAPS J. 2017;19:1071–1083.
  • D'Mello SR, Cruz CN, Chen ML, et al. The evolving landscape of drug products containing nanomaterials in the United States. Nat Nanotechnol. 2017;12:523–529.
  • Gaspar R, Duncan R. Polymeric carriers: preclinical safety and the regulatory implications for design and development of polymer therapeutics. Adv Drug Del Rev. 2009;61:1220–1231.
  • Kapoor M, Lee SL, Tyner KM. Liposomal drug product development and quality: current US experience and perspective. AAPS J. 2017;19:632–641.
  • EMA. EMA Reflection paper on the data requirements for intravenous liposomal products developed with reference to an innovator liposomal product. [Internet]; 2013. [cited 28 Jul 2017]. Available from: www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/03/WC500140351.pdf.
  • Chen ML, John M, Lee SL, et al. Development considerations for nanocrystal drug products. AAPS J. 2017;19:642–651.
  • EMA Joint MHLW. Joint MHLW. EMA reflection paper on the development of block copolymer micelle medicinal products. [Internet]; 2013. [cited 28 Jul 2017]. Available from: www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/02/WC500138390.pdf.
  • Tyner KM, Zou P, Yang X, et al. Product quality for nanomaterials: current U.S. experience and perspective. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2015;7:640–654.
  • Schellekens H, Stegemann S, Weinstein V, et al. How to regulate nonbiological complex drugs (NBCD) and their follow-on versions: points to consider. AAPS J. 2014;16:15–21.
  • Hussaarts L, Mühlebach S, Shah VP, et al. Equivalence of complex drug products: advances in and challenges for current regulatory frameworks. Ann NY Acad Sci. Forthcoming. [cited 2017 Apr 26]. doi: 10.1111/nyas.13347.
  • Oberdörster G, Oberdörster E, Oberdörster J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect. 2005;113:823–839.
  • Kamel Boulos MN, Le Blond J. On the road to personalised and precision geomedicine: medical geology and a renewed call for interdisciplinarity. Int J Health Geogr. 2016;15:5.
  • Duncan R. Nanomedicine(s) and their regulation: an overview. In: Fadeel B, editor. Handbook of safety assessment of nanomaterials – from toxicological testing to personalized medicine. Singapore: Pan Stanford Publishing Pte. Ltd; 2015. p. 1–41.
  • Crist RM, Grossman JH, Patri AK, et al. Common pitfalls in nanotechnology: lessons learned from NCI's nanotechnology characterization laboratory. Integr Biol (Camb). 2013;5:66–73.
  • Zamboni WC, Torchilin V, Patri AK, et al. Best practices in cancer nanotechnology: perspective from NCI nanotechnology alliance. Clin Cancer Res. 2014;18:3229–3241.
  • Schell RF, Sidone BJ, Caron WP, et al. Meta-analysis of inter-patient pharmacokinetic variability of liposomal and non-liposomal anticancer agents. Nanomedicine. 2014;10:109–117.
  • Harrison RK. The high drug attrition rate, 90–95% of drugs entering clinical development fail, is regularly discussed (Phase II and phase III failures: 2013–2015. Nat Rev Drug Discov. 2016;15:817–818.
  • Mullard A. 2016 EMA drug approval recommendations. Nat Rev Drug Discov. 2017;16:77.
  • Mullard A. 2016 FDA drug approvals. Nat Rev Drug Discov. 2017;16:73–76.
  • Scannell JW, Bosley J. When quality beats quantity: decision theory, drug discovery, and the reproducibility crisis. PLoS One. 2016;11:e0147215.
  • Dowdy SF. Overcoming cellular barriers for RNA therapeutics. Nat Biotechnol. 2017;35:222–229.
  • Bass AS. A historical view and vision into the future of the field of safety pharmacology. Handb Exp Pharmacol. 2015;229:3–45.
  • Collins AR, Annangi B, Rubio L, et al. High throughput toxicity screening and intracellular detection of nanomaterials. Wires Nanomed Nanobiotechnol. 2017;9:e1413.
  • Drews J. Drug discovery: a historical perspective. Science. 2000;287:1960–1964.
  • Munos B. Lessons from 60 years of pharmaceutical innovation. Nat Rev Drug Discov. 2009;8:959–968.
  • Torre BG, Albericio F. The pharmaceutical industry in 2016. An analysis of FDA drug approvals from a perspective of the molecule type. Molecules. 2017;22:368.
  • Mahmood I. Pharmacokinetic considerations in designing pediatric studies of proteins, antibodies, and plasma-derived products. Am J Therap. 2016;23:e1043–e1056.
  • Freedman LP, Gibson MC. The impact of preclinical irreproducibility on drug development. Clin Pharmacol Ther. 2015;97:16–18.
  • Begley CG, Ellis LM. Drug development: raise standards for preclinical cancer research. Nature. 2012;483:531–533.
  • Horvath P, Aulner N, Bickle M, et al. Screening out irrelevant cell-based models of disease. Nat Rev Drug Discov. 2016;15:751–769.
  • Loadman PM, Bibby MC, Double JA, et al. Pharmacokinetics of PK1 and doxorubicin in experimental colon tumor models with differing responses to PK1. Clin Cancer Res. 1999;5:3682–3688.
  • Duncan R, Sat-Klopsch Y-N, Burger AM, et al. Validation of tumour models for use in anticancer nanomedicine evaluation: the EPR effect and cathepsin B-mediated drug release rate. Cancer Chemother Pharmacol. 2013;72:417–427.
  • PricewaterhouseCoopers. Pharma 2020: The vision Which path will you take? [Internet]; 2007. [cited 28 Jul 2017]. Available from: http://www.pwc.com/gx/en/industries/pharmaceuticals-life-sciences/pharma-2020/pharma-2020-vision-path.html.
  • Yu LX, Amidon G, Khan MA, et al. Understanding pharmaceutical quality by design. AAPS J. 2014;16:771–783.
  • Crosby P. Quality is free: the art of making quality certain. New York: McGraw Hill; 1979.
  • Rathore AS, Winkle H. Quality by design for biopharmaceuticals. Nat Biotechnol. 2009;27:26–34.
  • Zuckerman JE, Gritli I, Tolcher A, et al. Correlating animal and human phase Ia/Ib clinical data with CALAA-01, a targeted, polymer-based nanoparticle containing siRNA. Proc Natl Acad Sci USA. 2014;111:11449–11454.
  • Duncan R, Spreafico F. Polymer conjugates. Pharmacokinetic considerations for design and development. Clin Pharmacokinet. 1994;27:290–306.
  • Duncan R. Polymer conjugates as anticancer nanomedicines. Nat Rev Cancer. 2006;6:688–701.
  • Duncan R, Cable HC, Lloyd JB, et al. Degradation of side-chains of N-(2-hydroxypropyl)methacrylamide copolymers by lysosomal thiol-proteinases. Biosci Rep. 1983;2:1041–1046.
  • Shaffer SA, Baker-Lee C, Kennedy J, et al. In vitro and in vivo metabolism of paclitaxel poliglumex: identification of metabolites and active proteases. Cancer Chemother Pharmacol. 2007;59:537–548.
  • Langer CJ, O'Byrne KJ, Socinski MA, et al. Phase III trial comparing paclitaxel poliglumex (CT-2103, PPX) in combination with carboplatin versus standard paclitaxel and carboplatin in the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer. J Thorac Oncol. 2008;3:623–630.
  • Perez EA, Awada A, O'Shaughnessy J, et al. Phase III trial of etirinotecan pegol (EP) versus Treatment of Physician’s Choice (TPC) in patients (pts) with advanced breast cancer (aBC) whose disease has progressed following anthracycline (A), taxane (T) and capecitabine (C): The BEACON study. J Clin Oncol. 2015;33:1001.
  • Seymour LW, Ulbrich K, Styger PS, et al. Tumour tropism and anti-cancer efficacy of polymer-based doxorubicin prodrugs in the treatment of subcutaneous murine B16F10 melanoma. Br J Cancer. 1994;70:636–641.
  • Sarapa N, Britto MR, Speed W, et al. Assessment of normal and tumor tissue uptake of MAG-CPT, a polymer-bound prodrug of camptothecin, in patients undergoing elective surgery for colorectal carcinoma. Cancer Chemother Pharmacol. 2003;52:424–430.
  • Harrington KJ, Mohammadtaghi S, Uster PS, et al. Effective targeting of solid tumors in patients with locally advanced cancers by radiolabeled pegylated liposomes. Clin Cancer Res. 2001;7:243–254.
  • La-Beck NM, Gabizon AA. Nanoparticle interactions with the immune system: clinical implications for liposome-based cancer chemotherapy. Front Immunol. 2017;68:416.
  • Lee H, Shields AF, Siegel BA, et al. 64Cu-MM-302 positron emission tomography quantifies variability of enhanced permeability and retention of nanoparticles in relation to treatment response in patients with metastatic breast cancer. Clin Cancer Res. 2017. Forthcoming. [cited 2017 Jun 7]. doi: 10.1158/1078-0432.CCR-16-3193.
  • Castaigne S, Pautas C, Terré C, et al. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012;379:1508–1516.
  • Khan N, Hills RK, Virgo P. Expression of CD33 is a predictive factor for effect of gemtuzumab ozogamicin at different doses in adult acute myeloid leukaemia. Leukemia. 2017;31:1059–1068.
  • Deslandes A. Comparative clinical pharmacokinetics of antibody-drug conjugates in first-in-human Phase 1 studies. MAbs. 2014;6:859–870.
  • Diamantis N, Banerji U. Antibody-drug conjugates-an emerging class of cancer treatment. Br J Cancer. 2016;114:362–367.
  • Barok M, Joensuu H, Isola J. Trastuzumab emtansine: mechanisms of action and drug resistance. Breast Cancer Res. 2014;16:209.
  • Duncan R, Lloyd JB. Pinocytosis in the rat visceral yolk sac. Effects of temperature, metabolic inhibitors and some other modifiers. Biochim Biophys Acta. 1978;544:647–655.
  • Mosesson Y, Mills GB, Yarden Y. Derailed endocytosis: an emerging feature of cancer. Nat Rev Cancer. 2008;8:835–850.
  • Lanzetti L, Di Fiore PP. Behind the scenes: endo/exocytosis in the acquisition of metastatic traits. Cancer Res. 2017;77:1813–1817.
  • Juliano RL. The delivery of therapeutic oligonucleotides. Nucleic Acids Res. 2016;44:6518–6548.
  • Maeda H, Takeshita J, Kanamaru R. A lipophilic derivative of neocarzinostatin. A polymer conjugation of an antitumor protein antibiotic. Int J Pept Protein Res. 1979;14:81–87.
  • Maeda H, Sawa T, Konno T. Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS. J Control Rel. 2001;74:47–61.
  • Breslow DS, Edwards EI, Newburg NR. Divinyl ether-maleic anhydride (pyran) copolymer used to demonstrate the effect of molecular weight on biological activity. Nature. 1973;246:160–162.
  • Regelson W. Future direction of synthetic polyanions (pyran copolymer). Cancer Treat Rep. 1978;62:1853–1856.
  • Ferguson EL, Duncan R. Dextrin-phospholipase A2: a novel bioresponsive anticancer conjugate. Biomacromolecules. 2009;10:1358–1364.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.