Administration, distribution, metabolism and elimination of polymer therapeutics

Journal of Controlled Release

Volumn 161, Issue 2, 2012, Pages 446-460

  Markovsky, Ela ^a   Baabur Cohen, Hemda ^a   Eldar Boock, Anat ^a   Omer, Liora ^a   Tiram, Galia ^a   Ferber, Shiran ^a   Ofek, Paula ^a   Polyak, Dina ^a   Scomparin, Anna ^a   Satchi Fainaro, Ronit ^a  

^a TEL AVIV UNIVERSITY   (Israel)

Author keywords

ADME; Angiogenesis; Angiogenesis dependent diseases; Biodistribution; Cancer; Polymer therapeutics

Indexed keywords

ADME; ANGIOGENESIS; BIODISTRIBUTIONS; CANCER; POLYMER THERAPEUTICS;

DEGRADATION; DRUG DELIVERY; METABOLISM; PHYSIOLOGY;

FUNCTIONAL POLYMERS;

CASPASE; CATHEPSIN B; CATHEPSIN D; CATHEPSIN H; CATHEPSIN K; CATHEPSIN L; CATHEPSIN S; CHITOSAN; COLLAGENASE 3; COPOLYMER; DEXAMETHASONE; DEXTRAN; GELATINASE A; GELATINASE B; HISTONE DEACETYLASE; HPMA COPOLYMER; LEGUMAIN; MACROGOL; MATRILYSIN; NALOXONE; NANOCARRIER; NKTR 118; OPIATE ANTAGONIST; PEGADEMASE; PEGINTERFERON ALPHA2A; PEGINTERFERON ALPHA2B; POLYAMIDOAMINE; POLYGLUTAMIC ACID; POLYMER; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANGIOGENESIS; APOPTOSIS; AUTOIMMUNE DISEASE; BIODEGRADABILITY; BONE METASTASIS; BRAIN ISCHEMIA; BREAST CANCER; BREAST TUMOR; CANCER INVASION; CHRONIC OBSTRUCTIVE LUNG DISEASE; COLON CANCER; COLON TUMOR; DRUG CONJUGATION; DRUG DEGRADATION; DRUG DELIVERY SYSTEM; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG FORMULATION; DRUG METABOLISM; DRUG RELEASE; EYE DISEASE; HEART FAILURE; HEMATOLOGIC MALIGNANCY; HYPOXIA; IMMUNE RESPONSE; INFLAMMATION; INJECTION; INTERNALIZATION; INTESTINE CELL; INTESTINE ULCER; INTRAMUSCULAR DRUG ADMINISTRATION; INTRAVENOUS DRUG ADMINISTRATION; LIVER METASTASIS; LUNG CANCER; MOLECULAR WEIGHT; MULTIPLE SCLEROSIS; OSTEOARTHRITIS; OSTEOPOROSIS; PATIENT COMPLIANCE; PHARMACODYNAMICS; PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROSTATE TUMOR; PROTEIN EXPRESSION; PSORIASIS; REVIEW; RHEUMATOID ARTHRITIS; SOLID TUMOR; STOMACH CANCER; STOMACH TUMOR; SUBCUTANEOUS DRUG ADMINISTRATION; TRAUMATIC BRAIN INJURY; UTERINE CERVIX TUMOR;

ANIMALS; DRUG CARRIERS; HUMANS; POLYMERS;

EID: 84862675929     PISSN: 01683659     EISSN: 18734995     Source Type: Journal    
DOI: 10.1016/j.jconrel.2011.12.021     Document Type: Review

References (188)

1. H. Jatzkewits, Peptamin (glycyl-L-leucyl-mescaline) bound to blood plasma expander (polyvinylpyrrolidone) as a new depot form of a biologically active primary amine (mescaline), Z. NatuNaturforsch. 10b (1955) 27-31.
2. J. Kopecek, P. Kopeckova, Design of polymer-drug conjugates, in: F. Kratz, P. Senter, H. Steinhagen (Eds.), Drug Delivery in Oncology, WILEY-VCH, 2011, pp. 485-512.
3. N.I. Givental, S.N. Ushakov, E.F. Panarin, G.O. Popova, Experimental studies on penicillin polymer derivatives, Antibiotiki 10 (1965) 701-706.
4. K.I. Shumikhina, E.F. Panarin, S.N. Ushakov, Experimental study of polymer salts of penicillins, Antibiotiki 11 (1966) 767-770.
5. H. Ringsdorf, Structure and properties of pharmacologically active polymers, J. Polym. Sci. (1975) 135-153.
6. A. Godwin, K. Bolina, M. Clochard, E. Dinand, S. Rankin, S. Simic, S. Brocchini, New strategies for polymer development in pharmaceutical science - a short review, J. Pharm. Pharmacol. 53 (2001) 1175-1184.
7. M. Kovar, L. Kovar, V. Subr, T. Etrych, K. Ulbrich, T. Mrkvan, J. Loucka, B. Rihova, HPMA copolymers containing doxorubicin bound by a proteolytically or hydrolytically cleavable bond: comparison of biological properties in vitro, J. Control. Release 99 (2004) 301-314.
8. R. Satchi-Fainaro, R. Duncan, C.M. Barnes, Polymer therapeutics for cancer: current status and future challenges, in: R. Satchi-Fainaro, R. Duncan (Eds.), Polymer Therapeutics II Polymers as Drugs, Conjugates and Gene delivery systems, Springer-Verlag, Heidelberg, Germany, 2006, pp. 1-65.
9. R. Duncan, The dawning era of polymer therapeutics, Nat. Rev. Drug Discov. 2 (2003) 347-360.
10. T. Yamaoka, Y. Tabata, Y. Ikada, Fate of water-soluble polymers administered via different routes, J. Pharm. Sci. 84 (1995) 349-354.
11. E. Lee, J. Lee, S. Jon, A novel approach to oral delivery of insulin by conjugating with low molecular weight chitosan, Bioconjug Chem 21 (2010) 1720-1723.
12. E. Lee, H. Kim, I.H. Lee, S. Jon, In vivo antitumor effects of chitosan-conjugated docetaxel after oral administration, J. Control. Release 140 (2009) 79-85.
13. E. Lee, J. Lee, I.-H. Lee, M. Yu, H. Kim, S.Y. Chae, S. Jon, Conjugated chitosan as a novel platform for oral delivery of paclitaxel, J. Med. Chem. 51 (2008) 6442-6449.
14. L. Diego, R. Atayee, P. Helmons, G. Hsiao, C.F. von Gunten, Novel opioid antagonists for opioid-induced bowel dysfunction, Expert Opin. Investig. Drugs 20 (2011) 1047-1056.
15. Nektar corporation website, http://www.nektar.com/product-pipeline/cns- pain-oral-nktr-118and119.html2011.
16. R. Wiwattanapatapee, B. Carreno-Gomez, N. Malik, R. Duncan, Anionic PAMAM dendrimers rapidly cross adult rat intestine in vitro: a potential oral delivery system? Pharm. Res. 17 (2000) 991-998.
17. B. Slutter, S.M. Bal, I. Que, E. Kaijzel, C. Lowik, J. Bouwstra, W. Jiskoot, Antigen-adjuvant nanoconjugates for nasal vaccination: an improvement over the use of nanoparticles? Mol. Pharm. 7 (2010) 2207-2215.
18. G. Gaucher, P. Satturwar, M.C. Jones, A. Furtos, J.C. Leroux, Polymeric micelles for oral drug delivery, Eur. J. Pharm. Biopharm. 76 (2010) 147-158.
19. K. Nagpal, S.K. Singh, D.N. Mishra, Chitosan nanoparticles: a promising system in novel drug delivery, Chem. Pharm. Bull. (Tokyo) 58 (2010) 1423-1430.
20. C.M. Lopes, P. Martins-Lopes, E.B. Souto, Nanoparticulate carriers (NPC) for oral pharmaceutics and nutraceutics, Pharmazie 65 (2010) 75-82.
21. K. Phua, K.W. Leong, Microscale oral delivery devices incorporating nanoparticles, Nanomedicine (Lond.) 5 (2010) 161-163.
22. T.W.Wong, Design of oral insulin delivery systems, J. Drug Target. 18 (2010) 79-92.
23. E. Segal, R. Satchi-Fainaro, Design and development of polymer conjugates as anti-angiogenic agents, Adv. Drug Deliv. Rev. 61 (2009) 1159-1176.
24. R. Gaspar, R. Duncan, Polymeric carriers: preclinical safety and the regulatory implications for design and development of polymer therapeutics, Adv. Drug Deliv. Rev. 61 (2009) 1220-1231.
25. H. Baabur-Cohen, L. Omer, R. Satchi-Fainaro, Recent progress in polymer therapeutics as nanomedicines, in: D. Peer (Ed.), Handbook of Harnessing biomaterials in Nanomedicine: Preparation, toxicity and applications, Pan Stanford Publishing Pte. Ltd., Hackensack, NJ, USA, 2011, pp. 77-122.
26. A. Eldar-Boock, D. Polyak, R. Satchi-Fainaro, Ligand-assisted vascular targeting of polymer therapeutics, in: F. Kratz, P. Senter (Eds.), Drug Delivery in Oncology - From Basic Research to Cancer Therapy, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2011.
27. Y. Geng, P. Dalhaimer, S.S. Cai, R. Tsai, M. Tewari, T. Minko, D.E. Discher, Shape effects of filaments versus spherical particles in flow and drug delivery, Nat. Nanotechnol. 2 (2007) 249-255.
28. R.A. Petros, J.M. DeSimone, Strategies in the design of nanoparticles for therapeutic applications, Nat. Rev. Drug Discov. 9 (2010) 615-627.
29. J. Fang, H. Nakamura, H. Maeda, The EPR effect: unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect, Adv. Drug Deliv. Rev. 63 (2011) 136-151.
30. Y. Matsumura, H. Maeda, A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs, Cancer Res. 46 (1986) 6387-6392.
31. P.A. Vasey, S.B. Kaye, R.Morrison, C. Twelves, P.Wilson, R. Duncan,A.H. Thomson, L.S. Murray, T.E. Hilditch, T.Murray, S. Burtles, D. Fraier, E. Frigerio, J. Cassidy, 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. Cancer Research Campaign Phase I/II Committee, Clin. Cancer Res. 5 (1999) 83-94.
32. J. Folkman, Angiogenesis: an organizing principle for drug discovery? Nat. Rev. Drug Discov. 6 (2007) 273-286.
33. X.M. Liu, S.C. Miller, D. Wang, Beyond oncology-application of HPMA copolymers in non-cancerous diseases, Adv. Drug Deliv. Rev. 62 (2010) 258-271.
34. J. Sanchis, F. Canal, R. Lucas, M.J. Vicent, Polymer-drug conjugates for novel molecular targets, Nanomedicine (Lond.) 5 (2010) 915-935.
35. F. Alexis, E. Pridgen, L.K. Molnar, O.C. Farokhzad, Factors affecting the clearance and biodistribution of polymeric nanoparticles, Mol. Pharm. 5 (2008) 505-515.
36. T. Schluep, J. Cheng, K.T. Khin, M.E. Davis, Pharmacokinetics and biodistribution of the camptothecin-polymer conjugate IT-101 in rats and tumor-bearing mice, Cancer Chemother. Pharmacol. 57 (2006) 654-662.
37. S.D. Perrault, C. Walkey, T. Jennings, H.C. Fischer, W.C.W. Chan, Mediating tumor targeting efficiency of nanoparticles through design, Nano Lett. 9 (2009) 1909-1915.
38. M. Saad, O.B. Garbuzenko, E. Ber, P. Chandna, J.J. Khandare, V.P. Pozharov, T. Minko, Receptor targeted polymers, dendrimers, liposomes: which nanocarrier is the most efficient for tumor-specific treatment and imaging? J. Control. Release 130 (2008) 107-114.
39. M. Barz, F. Canal, K. Koynov, R. Zentel, M.J. Vicent, Synthesis and in vitro evaluation of defined HPMA folate conjugates: influence of aggregation on folate receptor (FR) mediated cellular uptake, Biomacromolecules 11 (2010) 2274-2282.
40. E. Simone, B.S. Ding, V. Muzykantov, Targeted delivery of therapeutics to endothelium, Cell Tissue Res. 335 (2009) 283-300.
41. C. Fischbach, D.J. Mooney, Polymers for pro- and anti-angiogenic therapy, Biomaterials 28 (2007) 2069-2076.
42. H. Kobayashi, K.C. Boelte, P.C. Lin, Endothelial cell adhesion molecules and cancer progression, Curr. Med. Chem. 14 (2007) 377-386.
43. M. Jensen, F. Berthold, Targeting the neural cell adhesion molecule in cancer, Cancer Lett. 258 (2007) 9-21.
44. Z.M. Qian, H. Li, H. Sun, K. Ho, Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway, Pharmacol. Rev. 54 (2002) 561-587.
45. A. Gabizon, H. Shmeeda, H. Baabur, R. Satchi-Fainaro, Targeting the folate receptor with liposomes and polymer therapeutics, in: C. Leamon, A. Jackman (Eds.), Targeted Drug Strategies for Cancer and Inflammation, Springer-Verlag, Heidelberg, Germany, 2011, pp. 217-247.
46. R. Pasqualini, E. Koivunen, R. Kain, J. Lahdenranta, M. Sakamoto, A. Stryhn, R.A. Ashmun, L.H. Shapiro, W. Arap, E. Ruoslahti, Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis, Cancer Res. 60 (2000) 722-727.
47. M.D. Pierschbacher, E. Ruoslahti, Variants of the cell recognition site of fibronectin that retain attachment-promoting activity, Proc. Natl. Acad. Sci. U. S. A. 81 (1984) 5985-5988.
48. L.W. Seymour, D.R. Ferry, D. Anderson, S. Hesslewood, P.J. Julyan, R. Poyner, J. Doran, A.M. Young, S. Burtles, D.J. Kerr, Hepatic drug targeting: phase I evaluation of polymer-bound doxorubicin, J. Clin. Oncol. 20 (2002) 1668-1676.
49. K. Ulbrich, T. Etrych, P. Chytil, M. Jelinkova, B. Rihova, Antibody-targeted polymer-doxorubicin conjugates with pH-controlled activation, J. Drug Target. 12 (2004) 477-489.
50. K. Miller, R. Erez, E. Segal, D. Shabat, R. Satchi-Fainaro, Targeting bone metastases with a bispecific anticancer and antiangiogenic polymer-alendronate-taxane conjugate, Angew. Chem. Int. Ed. Engl. 48 (2009) 2949-2954.
51. E. Segal, H. Pan, P. Ofek, T. Udagawa, P. Kopeckova, J. Kopecek, R. Satchi-Fainaro, Targeting angiogenesis-dependent calcified neoplasms using combined polymer therapeutics, PLoS One 4 (2009) e5233.
52. D.E. Owens III, N.A. Peppas, Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles, Int. J. Pharm. 307 (2006) 93-102.
53. W. Jiskoot, R.M. van Schie, M.G. Carstens, H. Schellekens, Immunological risk of injectable drug delivery systems, Pharm. Res. 26 (2009) 1303-1314.
54. A.W. Richter, E. Akerblom, Polyethylene-glycol reactive antibodies in man - titer distribution in allergic patients treated with monomethoxy polyethylene-glycol modified allergens or placebo, and in healthy blood-donors, Int. Arch. Allergy Immunol. 74 (1984) 36-39.
55. J.K. Armstrong, G. Hempel, S. Koling, L.S. Chan, T. Fisher, H.J.Meiselman, G. Garratty, Antibody against poly(ethylene glycol) adversely affects PEG-asparaginase therapy in acute lymphoblastic leukemia patients, Cancer-Am. Cancer Soc. 110 (2007) 103-111.
56. N.J. Ganson, S.J. Kelly, E. Scarlett, J.S. Sundy, M.S. Hershfield, 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. 8 (2006).
57. A.A. van der Eijk, J.M. Vrolijk, B.L. Haagmans, Antibodies neutralizing peginterferon alfa during retreatment of hepatitis C, N. Engl. J. Med. 354 (2006) 1323-1324.
58. M. Pidaparti, B. Bostrom, Comparison of allergic reactions to pegasparaginase given intravenously versus intramuscularly, Pediatr. Blood Cancer (2011), doi:10.1002/pbc.23380.
59. J. Kopecek, P. Kopeckova, T. Minko, Z.R. Lu, HPMA copolymer-anticancer drug conjugates: design, activity, and mechanism of action, Eur. J. Pharm. Biopharm. 50 (2000) 61-81.
60. L. Kanerva, R. Jolanki, T. Estlander, 10 years of patch testing with the (meth)acrylate series, Contact Dermatitis 37 (1997) 255-258.
61. Z. Panagi, A. Beletsi, G. Evangelatos, E. Livaniou, D.S. Ithakissios, K. Avgoustakis, Effect of dose on the biodistribution and pharmacokinetics of PLGA and PLGA-mPEG nanoparticles, Int. J. Pharm. 221 (2001) 143-152.
62. G. Pasut, F.M. Veronese, PEG conjugates in clinical development or use as anti-cancer agents: an overview, Adv. Drug Deliv. Rev. 61 (2009) 1177-1188.
63. R. Duncan, M.J. Vicent, Do HPMA copolymer conjugates have a future as clinically useful nanomedicines? A critical overview of current status and future opportunities, Adv. Drug Deliv. Rev. 62 (2010) 272-282.
64. Y. Takakura, T. Fujita, M. Hashida, H. Sezaki, Disposition characteristics of macro-molecules in tumor-bearing mice, Pharm. Res. 7 (1990) 339-346.
65. A. Gabizon, F. Martin, Polyethylene glycol-coated (pegylated) liposomal doxorubicin. Rationale for use in solid tumours, Drugs 54 (1997) 15-21.
66. P. Caliceti, O. Schiavon, F.M. Veronese, Biopharmaceutical properties of uricase conjugated to neutral and amphiphilic polymers, Bioconjug Chem 10 (1999) 638-646.
67. T. Lammers, R. Kuhnlein, M. Kissel, V. Subr, T. Etrych, R. Pola, M. Pechar, K. Ulbrich, G. Storm, P. Huber, P. Peschke, Effect of physicochemical modification on the biodistribution and tumor accumulation of HPMA copolymers, J. Control. Release 110 (2005) 103-118.
68. F.M. Veronese, O. Schiavon, G. Pasut, R. Mendichi, L. Andersson, A. Tsirk, J. Ford, G. Wu, S. Kneller, J. Davies, R. Duncan, PEG-doxorubicin conjugates: influence of polymer structure on drug release, in vitro cytotoxicity, biodistribution, and antitumor activity, Bioconjug Chem 16 (2005) 775-784.
69. S. Danhauser-Riedl, E. Hausmann, H.D. Schick, R. Bender, H. Dietzfelbinger, J. Rastetter, A.R. Hanauske, Phase I clinical and pharmacokinetic trial of dextran conjugated doxorubicin (AD-70, DOX-OXD), Invest. New Drugs 11 (1993) 187-195.
70. S.D. Chipman, F.B. Oldham, G. Pezzoni, J.W. Singer, Biological and clinical characterization of paclitaxel poliglumex (PPX, CT-2103), a macromolecular polymer-drug conjugate, Int. J. Nanomedicine 1 (2006) 375-383.
71. A.V. Yurkovetskiy, R.J. Fram, XMT-1001, a novel polymeric camptothecin prodrug in clinical development for patients with advanced cancer, Adv. Drug Deliv. Rev. 61 (2009) 1193-1202.
72. C.D. Conover, R.B. Greenwald, A. Pendri, C.W. Gilbert, K.L. Shum, Camptothecin delivery systems: enhanced efficacy and tumor accumulation of camptothecin following its conjugation to polyethylene glycol via a glycine linker, Cancer Chemother. Pharmacol. 42 (1998) 407-414.
73. B. Rihova, Immunomodulating activities of soluble synthetic polymer-bound drugs, Adv. Drug Deliv. Rev. 54 (2002) 653-674.
74. M.E. Eichhorn, S. Strieth, M. Dellian, Anti-vascular tumor therapy: recent advances, pitfalls and clinical perspectives, Drug Resist. Updat. 7 (2004) 125-138.
75. R. Haag, F. Kratz, Polymer therapeutics: concepts and applications, Angew. Chem. Int. Ed. Engl. 45 (2006) 1198-1215.
76. R. Satchi-Fainaro, M. Puder, J.W. Davies, H.T. Tran, D.A. Sampson, A.K. Greene, G. Corfas, J. Folkman, Targeting angiogenesis with a conjugate of HPMA copolymer and TNP-470, Nat. Med. 10 (2004) 255-261.
77. L. Chesler, D.D. Goldenberg, I.T. Seales, R. Satchi-Fainaro, M. Grimmer, R. Collins, C. Struett, K.N. Nguyen, G. Kim, T. Tihan, Y. Bao, R.A. Brekken, G. Bergers, J. Folkman, W.A.Weiss,Malignant progression and blockade of angiogenesis in amurine transgenic model of neuroblastoma, Cancer Res. 67 (2007) 9435-9442.
78. R. Satchi-Fainaro, R. Mamluk, L. Wang, S.M. Short, J.A. Nagy, D. Feng, A.M. Dvorak, H.F. Dvorak, M. Puder, D. Mukhopadhyay, J. Folkman, Inhibition of vessel permeability by TNP-470 and its polymer conjugate, caplostatin, Cancer Cell 7 (2005) 251-261.
79. A.L. Marschall, A. Frenzel, T. Schirrmann, M. Schungel, S. Dubel, Targeting antibodies to the cytoplasm, MAbs 3 (2011) 3-16.
80. I. Brasnjevic, H.W. Steinbusch, C. Schmitz, P. Martinez-Martinez, Delivery of peptide and protein drugs over the blood-brain barrier, Prog. Neurobiol. 87 (2009) 212-251.
81. S.A. Cryan, Carrier-based strategies for targeting protein and peptide drugs to the lungs, AAPS J. 7 (2005) E20-E41.
82. A. des Rieux, V. Fievez, M. Garinot, Y.J. Schneider, V. Preat, Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach, J. Control. Release 116 (2006) 1-27.
83. Y. Dorsett, T. Tuschl, siRNAs: applications in functional genomics and potential as therapeutics, Nat. Rev. Drug Discov. 3 (2004) 318-329.
84. P. Glue, J.W. Fang, R. Rouzier-Panis, C. Raffanel, R. Sabo, S.K. Gupta, M. Salfi, S. Jacobs, Pegylated interferon-alpha2b: pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy data. Hepatitis C Intervention Therapy Group, Clin. Pharmacol. Ther. 68 (2000) 556-567.
85. J.P. Magnusson, S. Bersani, S. Salmaso, C. Alexander, P. Caliceti, In situ growth of side-chain PEG polymers from functionalized human growth hormone - a new technique for preparation of enhanced protein-polymer conjugates, Bioconjug. Chem. 21 (2010) 671-678.
86. W. Gao, W. Liu, T. Christensen, M.R. Zalutsky, A. Chilkoti, In situ growth of a PEG-like polymer from the C terminus of an intein fusion protein improves pharmacokinetics and tumor accumulation, Proc. Natl. Acad. Sci. U. S. A. 107 (2010) 16432-16437.
87. W. Gao, W. Liu, J.A. Mackay, M.R. Zalutsky, E.J. Toone, A. Chilkoti, In situ growth of a stoichiometric PEG-like conjugate at a protein's N-terminus with significantly improved pharmacokinetics, Proc. Natl. Acad. Sci. U. S. A. 106 (2009) 15231-15236.
88. S. Jevsevar, M. Kunstelj, V.G. Porekar, PEGylation of therapeutic proteins, Biotechnol. J. 5 (2010) 113-128.
89. E.W. Ng, D.T. Shima, P. Calias, E.T. Cunningham Jr., D.R. Guyer, A.P. Adamis, Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease, Nat. Rev. Drug Discov. 5 (2006) 123-132.
90. N. Goel, S. Stephens, Certolizumab pegol, MAbs 2 (2010) 137-147.
91. E. Keystone,D.Heijde,D.Mason Jr., R. Landewe, R.V. Vollenhoven, B. Combe, P. Emery, V. Strand, P. Mease,C. Desai, K. Pavelka, Certolizumab pegol plusmethotrexate is significantly more effective than placebo plus methotrexate in active rheumatoid arthritis: findings of a fifty-two-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, Arthritis Rheum. 58 (2008) 3319-3329.
92. J. Smolen, R.B. Landewe, P. Mease, J. Brzezicki, D. Mason, K. Luijtens, R.F. van Vollenhoven, A. Kavanaugh, M. Schiff, G.R. Burmester, V. Strand, J. Vencovsky, D. van der Heijde, Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomised controlled trial, Ann. Rheum. Dis. 68 (2009) 797-804.
93. P. Carmeliet, R.K. Jain, Angiogenesis in cancer and other diseases, Nature 407 (2000) 249-257.
94. P. Vaupel, Pathophysiological and vascular characteristics of solid tumors in relation to drug delivery, Drug delivery in Oncology: From Basic Research to Cancer Therapy, Wiley, 2011.
95. D. Putnam, J. Kopecek, Polymer conjugates with anticancer activity, Biopolymers II 122 (1995) 55-123.
96. K. Ulbrich, J. Strohalm, V. Subr, D. Plocova, R. Duncan, B. Rihova, Polymeric conjugates of drugs and antibodies for site-specific drug delivery, Macromol. Symp. 103 (1996) 177-192.
97. F. Kratz, U. Beyer, M.T. Schutte, Drug-polymer conjugates containing acid-cleavable bonds, Crit. Rev. Ther. Drug Carrier Syst. 16 (1999) 245-288.
98. P.C.A. Rodrigues, T. Roth, H.H. Fiebig, C. Unger, R. Mulhaupt, F. Kratz, Correlation of the acid-sensitivity of polyethylene glycol daunorubicin conjugates with their in vitro antiproliferative activity, Bioorg. Med. Chem. 14 (2006) 4110-4117.
99. K. Ulbrich, V. Subr, Polymeric anticancer drugs with pH-controlled activation, Advanced Drug Delivery Reviews 56 (2004) 1023-1050.
100. G.M. Dubowchik, M.A. Walker, Receptor-mediated and enzyme-dependent targeting of cytotoxic anticancer drugs, Pharmacol. Therapeut. 83 (1999) 67-123.
101. F. Kratz, I.A. Muller, C. Ryppa, A. Warnecke, Prodrug strategies in anticancer chemotherapy, ChemMedChem 3 (2008) 20-53.
102. M.C. Brahimi-Horn, J. Chiche, J. Pouyssegur, Hypoxia signalling controls metabolic demand, Curr. Opin. Cell Biol. 19 (2007) 223-229.
103. R.A. Gatenby, R.J. Gillies, Why do cancers have high aerobic glycolysis? Nat. Rev. Cancer 4 (2004) 891-899.
104. J.Hu, P.E. Van den Steen,Q.X. Sang, G. Opdenakker,Matrixmetalloproteinase inhibitors as therapy for inflammatory and vascular diseases, Nat. Rev. Drug Discov. 6 (2007) 480-498.
105. D. Wang, S.C. Miller, X.M. Liu, B. Anderson, X.S. Wang, S.R. Goldring, Novel dexamethasone-HPMA copolymer conjugate and its potential application in treatment of rheumatoid arthritis, Arthritis Res. Ther. 9 (2007) R2.
106. J.A.J. Carmela Palermo, Cysteine cathepsin proteases as pharmacological targets in cancer, Trends Pharmacol. Sci. 29 (2008) 22-28.
107. J.D. Mott, Z. Werb, Regulation of matrix biology by matrix metalloproteinases, Curr. Opin. Cell Biol. 16 (2004) 558-564.
108. T.H. Vu, Z. Werb, Matrix metalloproteinases: effectors of development and normal physiology, Genes Dev. 14 (2000) 2123-2133.
109. J.F. Woessner Jr., MMPs and TIMPs-an historical perspective, Mol. Biotechnol. 22 (2002) 33-49.
110. J. Martel-Pelletier, D.J. Welsch, J.P. Pelletier, Metalloproteases and inhibitors in arthritic diseases, Best Pract. Res. Clin. Rheumatol. 15 (2001) 805-829.
111. J.A. Mengshol, K.S. Mix, C.E. Brinckerhoff, Matrix metalloproteinases as therapeutic targets in arthritic diseases: bull's-eye or missing the mark? Arthritis Rheum. 46 (2002) 13-20.
112. B.K. Pilcher, J.A. Dumin, B.D. Sudbeck, S.M. Krane, H.G. Welgus, W.C. Parks, The activity of collagenase-1 is required for keratinocyte migration on a type I collagen matrix, J. Cell Biol. 137 (1997) 1445-1457.
113. S.E. Dunsmore, U.K. Saarialho-Kere, J.D. Roby, C.L. Wilson, L.M. Matrisian, H.G. Welgus, W.C. Parks, Matrilysin expression and function in airway epithelium, J. Clin. Invest. 102 (1998) 1321-1331.
114. J. Fang, T. Seki, H. Maeda, Therapeutic strategies by modulating oxygen stress in cancer and inflammation, Adv. Drug Deliv. Rev. 61 (2009) 290-302.
115. T.P. Szatrowski, C.F. Nathan, Production of large amounts of hydrogen-peroxide by human tumor-cells, Cancer Res. 51 (1991) 794-798.
116. S.S. Mahajan, E. Deu, E.M. Lauterwasser, M.J. Leyva, J.A. Ellman, M. Bogyo, A.R. Renslo, A fragmenting hybrid approach for targeted delivery of multiple therapeutic agents to the malaria parasite, ChemMedChem 6 (2011) 415-419.
117. D. Putnam, J. Kopecek, Polymer conjugates with anticancer activity, Advances in Polymer Science, Springer-Verlag, Berlin Heidelberg, 1995, pp. 55-123.
118. S.A. Cartlidge, R. Duncan, J.B. Lloyd, P. Rejmanová, J. Kopeček, Soluble, crosslinked N-(2-hydroxypropyl)methacrylamide copolymers as potential drug carriers: pinocytosis by rat visceral yolk sacs and rat intestine cultured in vitro. Effect of molecular weight on uptake and intracellular degradation, J. Control. Release 3 (1986) 55-66.
119. S.E. Gratton, P.A. Ropp, P.D. Pohlhaus, J.C. Luft, V.J. Madden, M.E. Napier, J.M. DeSimone, The effect of particle design on cellular internalization pathways, Proc. Natl. Acad. Sci. U. S. A. 105 (2008) 11613-11618.
120. D. Bray, B.D. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter, Essential Cell Biology, Garland Publishing, New York, 1998.
121. S.S. Dharap, B. Qiu, G.C. Williams, P. Sinko, S. Stein, T. Minko, Molecular targeting of drug delivery systems to ovarian cancer by BH3 and LHRH peptides, J. Control. Release 91 (2003) 61-73.
122. M. Ehrlich, W. Boll, A. Van Oijen, R. Hariharan, K. Chandran, M.L. Nibert, T. Kirchhausen, Endocytosis by random initiation and stabilization of clathrin-coated pits, Cell 118 (2004) 591-605.
123. H.T. McMahon, E. Boucrot, Molecular mechanism and physiological functions of clathrin-mediated endocytosis, Nat. Rev. Mol. Cell Biol. 12 (2011) 517-533.
124. I. Mellman, Endocytosis and molecular sorting, Annu. Rev. Cell Dev. Biol. 12 (1996) 575-625.
125. J. Khandare, T. Minko, Polymer-drug conjugates: progress in polymeric prodrugs, Prog. Polym. Sci. 31 (2006) 359-397.
126. A. Di Pietro, G. Dayan, G. Conseil, E. Steinfels, T. Krell, D. Trompier, H. Baubichon-Cortay, J. Jault, P-glycoprotein-mediated resistance to chemotherapy in cancer cells: using recombinant cytosolic domains to establish structure-function relationships, Braz. J. Med. Biol. Res. 32 (1999) 925-939.
127. S.P. Cole, G. Bhardwaj, J.H. Gerlach, J.E. Mackie, C.E. Grant, K.C. Almquist, A.J. Stewart, E.U. Kurz, A.M. Duncan, R.G. Deeley, Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line, Science 258 (1992) 1650-1654.
128. L.A. Doyle, W. Yang, L.V. Abruzzo, T. Krogmann, Y. Gao, A.K. Rishi, D.D. Ross, A multidrug resistance transporter from human MCF-7 breast cancer cells, Proc. Natl. Acad. Sci. U. S. A. 95 (1998) 15665-15670.
129. T. Minko, P. Kopeckova, J. Kopecek, Chronic exposure to HPMA copolymer-bound adriamycin does not induce multidrug resistance in a human ovarian carcinoma cell line, J. Control. Release 59 (1999) 133-148.
130. T. Minko, P. Kopeckova, V. Pozharov, J. Kopecek, HPMA copolymer bound adriamycin overcomes MDR1 gene encoded resistance in a human ovarian carcinoma cell line, J. Control. Release 54 (1998) 223-233.
131. A. Nori, J. Kopecek, Intracellular targeting of polymer-bound drugs for cancer chemotherapy, Adv. Drug Deliv. Rev. 57 (2005) 609-636.
132. V.Omelyanenko, P. Kopeckova, C. Gentry, J. Kopecek, TargetableHPMA copolymer-adriamycin conjugates. Recognition, internalization, and subcellular fate, J. Control. Release 53 (1998) 25-37.
133. V. Russ, H. Elfberg, C. Thoma, J. Kloeckner, M. Ogris, E. Wagner, Novel degradable oligoethylenimine acrylate ester-based pseudodendrimers for in vitro and in vivo gene transfer, Gene Ther. 15 (2008) 18-29.
134. O. Boussif, F. Lezoualc'h, M.A. Zanta, M.D. Mergny, D. Scherman, B. Demeneix, J.P. Behr, A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine, Proc. Natl. Acad. Sci. 92 (1995) 7297-7301.
135. J.P. Behr, The proton sponge: a trick to enter cells the viruses did not exploit, Chimia 51 (1997) 34-36.
136. N.D. Sonawane, F.C. Szoka, A.S. Verkman, Chloride accumulation and swelling in endosomes enhances DNA transfer by polyamine-DNA polyplexes, J. Biol. Chem. 278 (2003) 44826-44831.
137. S.D. Li, L. Huang, Targeted delivery of siRNA by nonviral vectors: lessons learned from recent advances, Curr. Opin. Investig. Drugs 9 (2008) 1317-1323.
138. A.L. Jackson, S.R. Bartz, J. Schelter, S.V. Kobayashi, J. Burchard, M. Mao, B. Li, G. Cavet, P.S. Linsley, Expression profiling reveals off-target gene regulation by RNAi, Nat. Biotechnol. 21 (2003) 635-637.
139. A.D. Judge, V. Sood, J.R. Shaw, D. Fang, K. McClintock, I. MacLachlan, Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA, Nat. Biotechnol. 23 (2005) 457-462.
140. H. Kato, O. Takeuchi, S. Sato, M. Yoneyama, M. Yamamoto, K. Matsui, S. Uematsu, A. Jung, T. Kawai, K.J. Ishii, O. Yamaguchi, K. Otsu, T. Tsujimura, C.S. Koh, C. Reis e Sousa, Y. Matsuura, T. Fujita, S. Akira, Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses, Nature 441 (2006) 101-105.
141. M. Sioud, RNA interference and innate immunity, Adv. Drug Deliv. Rev. 59 (2007) 153-163.
142. A.L. Jackson, J. Burchard, D. Leake, A. Reynolds, J. Schelter, J. Guo, J.M. Johnson, L. Lim, J. Karpilow, K. Nichols, W. Marshall, A. Khvorova, P.S. Linsley, Positionspecific chemical modification of siRNAs reduces "off-target" transcript silencing, RNA 12 (2006) 1197-1205.
143. A.L. Jackson, J. Burchard, J. Schelter, B.N. Chau, M. Cleary, L. Lim, P.S. Linsley, Widespread siRNA "off-target" transcript silencing mediated by seed region sequence complementarity, RNA 12 (2006) 1179-1187.
144. A. Judge, I. MacLachlan, Overcoming the innate immune response to small interfering RNA, Hum. Gene Ther. 19 (2008) 111-124.
145. N.D. Rawlings, F.R. Morton, C.Y. Kok, J. Kong, A.J. Barrett, MEROPS: the peptidase database, Nucleic Acids Res. 36 (2008) D320-D325.
146. K. Brix, A. Dunkhorst, K. Mayer, S. Jordans, Cysteine cathepsins: cellular roadmap to different functions, Biochimie 90 (2008) 194-207.
147. S.P. Lutgens, K.B. Cleutjens, M.J. Daemen, S. Heeneman, Cathepsin cysteine proteases in cardiovascular disease, FASEB J. 21 (2007) 3029-3041.
148. M.M. Mohamed, B.F. Sloane, Cysteine cathepsins: multifunctional enzymes in cancer, Nat. Rev. Cancer 6 (2006) 764-775.
149. Y.J. Zhang, H. Fang, J. Jiao, W.F. Xu, The structure and function of histone deacetylases: the target for anti-cancer therapy, Curr. Med. Chem. 15 (2008) 2840-2849.
150. C. Liu, C.Z. Sun, H.N. Huang, K. Janda, T. Edgington, Overexpression of legumain in tumors is significant for invasion/metastasis and a candidate enzymatic target for prodrug therapy, Cancer Res. 63 (2003) 2957-2964.
151. L. Stern, R. Perry, P. Ofek, A. Many, D. Shabat, R. Satchi-Fainaro, A novel antitumor prodrug platform designed to be cleaved by the endoprotease legumain, Bioconjug. Chem. 20 (2009) 500-510.
152. L.W. Seymour, D.R. Ferry, D.J. Kerr, D. Rea, M. Whitlock, R. Poyner, C. Boivin, S. Hesslewood, C. Twelves, R. Blackie, A. Schatzlein, D. Jodrell, D. Bissett, H. Calvert, M. Lind, A. Robbins, S. Burtles, R. Duncan, J. Cassidy, Phase II studies of polymer-doxorubicin (PK1, FCE28068) in the treatment of breast, lung and colorectal cancer, Int. J. Oncol. 34 (2009) 1629-1636.
153. F. Kratz, K. Abu Ajaj, A. Warnecke, Anticancer carrier-linked prodrugs in clinical trials, Expert Opin. Investig. Drugs 16 (2007) 1037-1058.
154. K.S. Albain, C.P. Belani, P. Bonomi, K.J. O'Byrne, J.H. Schiller, M. Socinski, PIONEER: a phase III randomized trial of paclitaxel poliglumex versus paclitaxel in chemotherapy-naive women with advanced-stage non-small-cell lung cancer and performance status of 2, Clin. Lung Cancer 7 (2006) 417-419.
155. P. Bonomi, Paclitaxel poliglumex (PPx, CT-2103): macromolecular medicine for advanced non-small-cell lung cancer, Expert Rev. Anticancer 7 (2007) 415-422.
156. L.S. Nair, C.T. Laurencin, Biodegradable polymers as biomaterials, Prog. Polym. Sci. 32 (2007) 762-798.
157. R. Mehvar, Dextrans for targeted and sustained delivery of therapeutic and imaging agents, J. Control. Release 69 (2000) 1-25.
158. V. Knorr, M. Ogris, E. Wagner, An acid sensitive ketal-based polyethylene glycololigoethylenimine copolymer mediates improved transfection efficiency at reduced toxicity, Pharm. Res. 25 (2008) 2937-2945.
159. K. Luo, J. Yang, P. Kopeckova, J. Kopecek, Biodegradablemultiblock poly[N-(2-hydroxypropyl) methacrylamide] via reversible addition-fragmentation chain transfer polymerization and click chemistry, Macromolecules 44 (2011) 2481-2488.
160. H. Pan, J. Yang, P. Kopeckova, J. Kopecek, Backbone degradable multiblock N-(2-hydroxypropyl)methacrylamide copolymer conjugates via reversible additionfragmentation chain transfer polymerization and thiol-ene coupling reaction, Biomacromolecules 12 (2011) 247-252.
161. J. Yang, K. Luo, H. Pan, P. Kopeckova, J. Kopecek, Synthesis of biodegradable multi-block copolymers by click coupling of RAFT-generated heterotelechelicPolyHPMA conjugates, React. Funct. Polym. 71 (2011) 294-302.
162. M. Barz, F.K. Wolf, F. Canal, K. Koynov, M.J. Vicent, H. Frey, R. Zentel, Synthesis, characterization and preliminary biological evaluation of P(HPMA)-b-P(LLA) copolymers: a new type of functional biocompatible block copolymer, Macromol. Rapid Commun. 31 (2010) 1492-1500.
163. L.W. Seymour, R. Duncan, J. Strohalm, J. Kopecek, Effect of molecular weight (Mw) of N-(2-hydroxypropyl)methacrylamide copolymers on body distribution and rate of excretion after subcutaneous, intraperitoneal, and intravenous administration to rats, J. Biomed. Mater. Res. 21 (1987) 1341-1358.
164. M.P. Bohrer, W.M. Deen, C.R. Robertson, J.L. Troy, B.M. Brenner, Influence of molecular configuration on the passage of macromolecules across the glomerular capillary wall, J. Gen. Physiol. 74 (1979) 583-593.
165. W.M. Deen, M.P. Bohrer, B.M. Brenner, Macromolecule transport across glomerular capillaries: application of pore theory, Kidney Int. 16 (1979) 353-365.
166. M. Kovar, J. Strohalm, T. Etrych, K. Ulbrich, B. Rihova, Star structure of antibody-targeted HPMA copolymer-bound doxorubicin: a novel type of polymeric conjugate for targeted drug delivery with potent antitumor effect, Bioconjug. Chem. 13 (2002) 206-215.
167. T. Yamaoka, Y. Tabata, Y. Ikada, Distribution and tissue uptake of poly(ethylene glycol) with different molecular-weights after intravenous administration to mice, J. Pharm. Sci. 83 (1994) 601-606.
168. L.W. Seymour, Y. Miyamoto, H. Maeda, M. Brereton, J. Strohalm, K. Ulbrich, R. Duncan, Influence of molecular weight on passive tumour accumulation of a soluble macromolecular drug carrier, Eur. J. Cancer 31A (1995) 766-770.
169. A. Al-Shamkhani, R. Duncan, Radioiodination of alginate via covalently-bound tyrosinamide allows monitoring of its fate in vivo, J. Bioact. Compat. Polym. 10 (1995) 4-13.
170. R.Webster, V. Elliott, B.K. Park, D.Walker, M. Hankin, P. Taupin, PEG and PEG conjugates toxicity: towards an understanding of the toxicity of PEG and its relevance to PEGylated biologicals, in: F.M. Veronese (Ed.), PEGylated Protein Drugs: Basic Science and Clinical Applications, Birkhauser Verlag, Switzerland, 2009, pp. 127-146.
171. R. Webster, E. Didier, P. Harris, N. Siegel, J. Stadler, L. Tilbury, D. Smith, PEGylated proteins: evaluation of their safety in the absence of definitive metabolism studies, Drug Metab. Dispos. 35 (2007) 9-16.
172. A. Bendele, J. Seely, C. Richey, G. Sennello, G. Shopp, Short communication: renal tubular vacuolation in animals treated with polyethylene-glycol-conjugated proteins, Toxicol. Sci. 42 (1998) 152-157.
173. M. Barz, R. Luxenhofer, R. Zentel, M.J. Vicent, Overcoming the PEG-addiction: well-defined alternatives to PEG, from structure-property relationships to better defined therapeutics, Polym. Chem.-Uk 2 (2011) 1900-1918.
174. D.G. Vartak, R.A. Gemeinhart, Matrix metalloproteases: Underutilized targets for drug delivery, J. Drug Target. 15 (2007) 1-20.
175. S. Lee, J. Xie, X. Chen, Activatable molecular probes for cancer imaging, Curr. Top Med. Chem. 10 (2010) 1135-1144.
176. L.E. Edington, A.B. Berger, G. Blum, V.E. Albrow, M.G. Paulick, N. Lineberry, M. Bogyo, Noninvasive optical imaging of apoptosis by caspase-targeted activity-based probes, Nat. Med. 15 (2009) 967-974.
177. C. Tung, U. Mahmood, S. Bredow, R. Weissleder, In vivo imaging of proteolytic enzyme activity using a novel molecular reporter, Cancer Res. 60 (2000) 4953-4958.
178. R. Duncan, H.C. Cable, J.B. Lloyd, P. Rejmanová, J. Kopecek, Polymers containing enzymatically degradable bonds, 7) design of oligopeptide side-chains in poly [N-(2-hydroxypropyl)methacrylamide] copolymers to promote efficient degradation by lysosomal enzymes, Macromol. Chem. Phys. 184 (1983) 1997-2008.
179. S. Wu, Y. Huang, C. Yeh, M. Tsai, C. Liao, W. Cheng, W. Chen, K. Lin, Cathepsin H regulated by the thyroid hormone receptors associate with tumor invasion in human hepatoma cells, Oncogene 30 (2011) 2057-2069.
180. C. Liu, C. Sun, H. Huang, K. Janda, T. Edgington, Overexpression of legumain in tumors is significant for invasion/metastasis and a candidate enzymatic target for prodrug therapy, Cancer Res. 63 (2003) 2957-2964.
181. C.A. Olsen, M.R. Ghadiri, Discovery of potent and selective histone deacetylase inhibitors via focused combinatorial libraries of cyclic α3β-tetrapeptides, J. Med. Chem. 52 (2009) 7836-7846.
182. J.G. Kiang, K.T. Tsen, Biology of hypoxia, Chin. J. Physiol. 49 (2006) 223-233.
183. Z. Zhang, J. Fan, P.P. Cheney, M. Berezin, Y., W.B. Edwards, W.J. Akers, D. Shen, K. Liang, J.P. Culver, S. Achilefu, Activatable molecular systems using homologous near-infrared fluorescent probes for monitoring enzyme activities in vitro, in cellulo, and in vivo., Mol. Pharm. 6 (2009) 416-427.
184. S.F. Larner, D.M. McKinsey, R.L. Hayes, K.K.W. Wang, Caspase 7: increased expression and activation after traumatic brain injury in rats, J. Neurochem. 94 (2005) 97-108.
185. H. Nagahara, K. Mimori, T. Utsunomiya, G. Barnard, M. Ohira, K. Hirakawa, M. Mori, Clinicopathologic and biological significance of kallikrein 6 overexpression in human gastric cancer, Clin. Cancer Res. 11 (2005) 6800-6806.
186. J.T. Kim, E.Y. Song, K.S. Chung, M.A. Kang, J.W. Kim, S.J. Kim, Y.I. Yeom, J.H. Kim, K.H. Kim, H.G. Lee, Up-regulation and clinical significance of serine protease kallikrein 6 in colon cancer, Cancer 117 (2011) 2608-2619.
187. N. Sharma, K. Oikonomopoulou, K. Ito, B. Renaux, E.P. Diamandis, M.D. Hollenberg, D.E. Rancourt, Substrate specificity determination of mouse implantation serine proteinase and human kallikrein-related peptidase 6 by phage display, Biol. Chem. 389 (2008) 1097-1105.
188. C.G. Laurent Brault, Franz Bracher, Kilian Huber, Stefan Knapp, Jürg Schwaller, PIM serine/threonine kinases in the pathogenesis and therapy of hematologic malignancies and solid cancers, Haematologica 95 (2010) 1004-1015.