Jindrich Kopecek
Czechoslovak Academy of Sciences
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Featured researches published by Jindrich Kopecek.
Biomaterials | 1989
Blanka Rihova; M. Bilej; V. Vetvicka; Karel Ulbrich; Jiří Strohalm; Jindrich Kopecek; Ruth Duncan
N-(2-hydroxypropyl)methacrylamide polymeric prodrugs containing adriamycin bound to polymers via glycylphenylalanylleucylglycine side chains and, in one case, galactosamine bound via the same sequence, were tested for immunogenicity after intravenous, subcutaneous and oral application in two inbred strains of mice. The serum antibody level was determined by enzyme-linked immunoassay on the 3rd and 6th day after the last treatment. It was found that antibodies were only produced in very small amounts. In some experimental groups, the antibody titres measured following administration of copolymer conjugate were comparable with those present in non-treated controls. Attachment of adriamycin to N-(2-hydroxypropyl)methacrylamide copolymer considerably decreased its toxicity against haematopoietic precursors in bone marrow as measured by the in vivo colony-forming unit-spleen assay and its ability to inhibit [3H] thymidine incorporation by mouse splenocytes and human peripheral blood lymphocytes measured in vitro.
Biochimica et Biophysica Acta | 1981
Ruth Duncan; Pavla Rejmanová; Jindrich Kopecek; John B. Lloyd
Synthetic 125I-labelled N-(2-hydroxypropyl)methacrylamide copolymers containing four different, potentially degradable peptidyl side chains were incubated with rat visceral yolk sacs cultured in vitro. All copolymers were captured by fluid-phase pinocytosis and three of the side chains were susceptible to lysosomal hydrolysis, resulting in release of [125I]iodotyrosine back into the culture medium. Uptake and degradation was completely inhibited by 2,4-dinitrophenol. The thiol-proteinase inhibitor leupeptin did not affect the rate of pinocytosis, but caused different degrees of inhibition of hydrolysis depending on side chain composition.
Archive | 1984
Jindrich Kopecek
Polymeric drugs are usually divided into two groups (1–3). The first group comprises polymers possessing physiological activity. Even though a repeating fragment whose presence is absolutely necessary for the physiological activity of the polymer can be identified also in these polymers, their low-molecular weight analogs do not usually possess physiological activity (2).
Journal of Controlled Release | 1989
Blanka Říhová; V. Větvička; J. Strohalm; Karel Ulbrich; Jindrich Kopecek
Abstract Splenocytes were removed from A/J mice 14 days after i.p. injection of 1 × 10 8 sheep red blood cells and were incubated for 10 min, 3 h and 5 days with free daunomycin, free anti Thy 1.2 antibodies or daunomycin conjugated to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates with biodegradable (Gly-Leu-Gly; Gly-Phe-Leu-Gly) or non-biodegradable (Gly-Gly) side-chains containing targeting anti Thy 1.2 antibodies. The effect on the antibody response, represented by decrease in the numbers of IgM and IgG plaque-forming, i.e., antibody-releasing mouse splenocytes (plaque-forming cells), was detected. It was shown that a 10 min contact of immunocompetent cells with daunomycin-HPMA copolymer conjugates is sufficient for suppression of antibody formation. However, 3 hours incubation were necessary to obtain significant decrease in a number of PFC. Lymphocytes (mouse splenocytes) were very sensitive to free daunomycin. Concentration of 50 μg/ml eliminated all lymphocytes from tissue culture. At 1–10 ug/ml, a high proportion of cells remained viable, but the antibody response was completely suppressed. A comparable amount of daunomycin (35–70 μg/ml) bound to copolymer with targeting antibodies did not kill lymphocytes in tissue culture, but the antibody response was substantially suppressed (50–90%). In all experiments IgG antibody formation was more sensitive to suppression than IgM response. Biodegradability of the bond between the HPMA copolymer carrier and daunomycin substantially increased the pharmacological effect although a certain degree of immunosuppression was detected with the drug conjugated to targeted non-biodegradable HPMA copolymer. Free daunomycin inhibited [ 3 H]thymidine incorporation by mouse T lymphocytes (cultivation in presence of Con A) at the concentration of 0.1 μg/ml. To achieve the same effect, 5 times more daunomycin bound to biodegradable HPMA copolymer with targeting anti Thy 1.2 antibodies or 500 times more daunomycin bound to non-targeted biodegradable HPMA copolymer was necessary.
Biochemical Pharmacology | 1989
Jim Cassidy; Ruth Duncan; Gilmour Morrison; Jiri Strohalm; Dana Plocova; Jindrich Kopecek; Stanley B. Kaye
Archive | 1976
Drahoslav Lim; Jindrich Kopecek; Hedvika Bazilova nee Sverinova; Jiri Vacik
Archive | 1975
J. Drobník; Jindrich Kopecek; Jiri Labsky; Pavla Rejmanová; J. Exner; J. Kálal
Anti-cancer Drug Design | 1987
Ruth Duncan; Leonard Charles Willia Seymour; P Kopeckova Rejmanova; Jindrich Kopecek
Bioscience Reports | 1982
Ruth Duncan; Hazel C. Cable; John B. Lloyd; Pavla Rejmanová; Jindrich Kopecek
Archive | 1975
Jindrich Kopecek; Karel Ulbrich; Jiri Vacik; Jiri Strohalm; Vladimir Chytry; J. Drobník; J. Kálal