Table 1.
Milestones in HPMA (co)polymer research.
| Year | Study | Publication |
|---|---|---|
| 1973 | First synthesis | J. Kopeček, H. Bažilová, Poly[N-(2-Hydroxypropyl)methacrylamide]. 1. Radical polymerization and copolymerization. Europ. Polym. J. 9 (1973) 7–14. |
| 1974 | Characterization of PHPMA solution properties | M. Bohdanecký, H. Bažilová, J. Kopeček, Poly[N-(2-Hydroxypropyl)methacrylamide]. II. Hydrodynamic properties diluted polymer solutions. Europ. Polym. J. 10 (1974) 405–410. |
| 1974 | First hydrogels | J. Kopeček, H. Bažilová, Poly[N-(2-Hydroxypropyl)methacrylamide]. III. Crosslinking copolymerization. Europ. Polym. J. 10 (1974) 465–470. |
| 1976 | First enzymatic release of ligand from a polymer conjugate in vitro | J. Drobník, J. Kopeček, J. Labský, P. Rejmanová, J. Exner, V. Saudek, J. Kálal, Enzymatic cleavage of side-chains synthetic water-soluble polymers. Makromol. Chem. 177 (1976) 2833–2848. |
| 1978 | First HPMA modified protein | V. Chytrý, A. Vrána, J. Kopeček, Synthesis and activity of a polymer which contains insulin covalently bound on a copolymer of N-(2-hydroxypropyl)methacrylamide and N-methacryloylglycylglycine 4-nitrophenyl ester. Makromol. Chem. 179 (1978) 329–336. |
| 1979 | First HPMA–drug conjugate | B. Obereigner, M. Burešová, A. Vrána, J. Kopeček, Preparation of polymerizable derivatives of N-(4-aminobenzenesulfonyl)-N′-butylurea. J. Polym. Sci. Polym. Symp. 66 (1979) 41–52. |
| 1981 | First enzymatic release of ligand from a polymeric substrate by a polymer-modified enzyme | J. Kopeček, P. Rejmanová, V. Chytrý, Polymers containing enzymatically degradable bonds 1. Chymotrypsincatalyzed hydrolysis of p-nitroanilides of phenylalanine and tyrosine attached to side-chains of copolymers of N-(2-hydroxypropyl)methacrylamide. Makromol. Chem. 182 (1981) 799–809. |
| 1981 | First enzymatic release of ligand from a polymer conjugate in vivo | J. Kopeček, I. Cífková, P. Rejmanová, J. Strohalm, B. Obereigner, K. Ulbrich, Polymers containing enzymatically degradable bonds. 4. Preliminary experiments in vivo. Makromol. Chem. 182 (1981) 2941–2949. |
| 1982 | First degradable hydrogels | K. Ulbrich, J. Strohalm, J. Kopeček, Polymers containing enzymatically degradable bonds. VI. Hydrophilic gels cleavable by chymotrypsin. Biomaterials 3 (1982) 150–154. |
| 1985 | First HPMA–drug–antibody conjugate | B. Říhová, J. Kopeček, Biological Properties of targetable poly[N-(2-hydroxypropy)methacrylamide]–antibody conjugates. J. Controlled Release 2 (1985) 289–310. |
| 1994 | First combination therapy using polymer-bound drugs | N.L. Krinick, Y. Sun, D. Jonyer, J.D. Spikes, R.C. Straight, J. Kopeček, A polymeric drug delivery system for the simultaneous delivery of drugs activatable by enzymes and/or light. J. Biomat. Sci. Polym. Ed. 5 (1994) 211–222. |
| 1995 | First semitelechelic HPMA | S. Kamei, J. Kopeček, Prolonged blood circulation in rats of nanospheres surface-modified with semitelechelic [N-(2-hydroxypropyl)methacrylamide]. Pharmaceutical Res. 12 (1995) 663–668. |
| 1999 | First clinical trials | 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, and on behalf of the Cancer Research Campaign Phase I/II Committee, 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) 83–94. |
| 1999 | First ATRP polymerization | M. Teodorescu, K. Matyjaszewski, Atom transfer radical polymerization of (meth)acrylamides. Macromolecules (1999) 4826–4831. |
| 1999 | First self-assembly into hybrid hydrogels | C. Wang, R.J. Stewart, J. Kopeček, Hybrid hydrogels assembled from synthetic polymers and coiled-coil protein domains. Nature 397 (1999) 417–420. |
| 2005 | First RAFT polymerization | C.W. Scales, Y.A. Vasilieva, A.J. Convertine, A.B. Lowe, C.L. McCormick, Direct, controlled synthesis of the nonimmunogenic, hydrophilic polymer, poly(N-(2-hydroxypropyl)methacrylamide) via RAFT in aqueous media. Biomacromolecules 6 (2005) 1846–1850. |
| 2009 | First self-assembly at cell surface | K. Wu, J. Liu, R.N. Johnson, J. Yang, J. Kopeček, Drug-free macromolecular therapeutics: induction of apoptosis coiled-coil mediated crosslinking of antigens at cell surface. Submitted |