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Dive into the research topics where Martin Hruby is active.

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Featured researches published by Martin Hruby.


Macromolecular Rapid Communications | 2012

Poly(2-Oxazoline)s – Are They More Advantageous for Biomedical Applications Than Other Polymers?

Ondrej Sedlacek; Bryn D. Monnery; Sergey K. Filippov; Richard Hoogenboom; Martin Hruby

Poly(2-alkyl-2-oxazoline)s are biocompatible polymers with polypeptide-isomeric structures that are attracting increasing interest as biomaterials for drug, gene, protein, and radionuclide delivery. They are, however, still relatively new in comparison to other classes of hydrophilic water-soluble polymers already established for such use, including poly(ethylene oxide), polyvinylpyrrolidone, and polymethacrylamides such as poly[N-(2-hydroxypropyl)methacrylamide]. This feature article critically compares the synthetic aspects and physicochemical and biological properties of poly(2-alkyl-2-oxazoline)s and these commonly studied polymers in terms of their suitability for biomedical applications.


Macromolecular Bioscience | 2010

Polyoxazoline Thermoresponsive Micelles as Radionuclide Delivery Systems

Martin Hruby; Sergey K. Filippov; Jiri Panek; Michaela Nováková; Hana Macková; Jan Kucka; David Vetvicka; Karel Ulbrich

Thermoresponsive polymer micelles are promising drug and radionuclide carriers with a strong passive targeting effect into solid tumors. We have synthesized ABA triblock copolymers poly[2-methyl-2-oxazoline-block-(2-isopropyl-2-oxazoline-co-2-butyl-2-oxazoline)-block-2-methyl-2-oxazoline]. These polymers are molecularly dissolved in aqueous millieu below the cloud point temperature (CPT) of the thermoresponsive central block and above CPT form polymer micelles at CMC 5-10 × 10(-5) g · mL(-1) with diameter ≈200 nm. The phenolic moiety introduced into the copolymer allowed radionuclide labeling with iodine-125 ongoing in good yield with sufficient in vitro stability under model conditions.


Bioconjugate Chemistry | 2009

Biological evaluation of polymeric micelles with covalently bound doxorubicin.

David Vetvicka; Martin Hruby; Ondrej Hovorka; Tomáš Etrych; Miroslav Vetrik; Lubomir Kovar; Marek Kovar; Karel Ulbrich; Blanka Rihova

The main limitation of contemporary anticancer chemotherapy remains to be the insufficient specificity of the drugs for tumor tissue, which decreases the maximum tolerated dose due to severe side effects. Micellar drug delivery systems based on amphiphilic block copolymers with a very narrow size distribution (10 to 100 nm in diameter) is a novel innovative approach. Here, we report biological and pharmacological properties of polymeric micellar conjugate containing doxorubicin (DOX) covalently bound via hydrolytically cleavable hydrazone bonds to the micelle core. The system had a very low systemic toxicity (almost 20 times lower than free DOX) and long circulation in the bloodstream (with half of the dose after 24 h). Significant accumulation of tested micelles within the tumor was confirmed by fluorescent whole body imaging. Our new micellar system showed promising therapeutic activity against established murine EL-4 T-cell lymphoma; it was found that it is able to completely cure about 75% of tumor-bearing mice (with doses of either 1 x 150 mg DOX kg(-1) or 2 x 75 mg DOX kg(-1), administered i.v.). Moreover, treatment with micelles in cured mice induced tumor-specific resistance. Up to 80% of these mice survived rechallenge with original but not with distinct tumor cells.


Macromolecular Bioscience | 2009

Thermoresponsive, Hydrolytically Degradable Polymer Micelles Intended for Radionuclide Delivery

Martin Hruby; Cestmir Konak; Jan Kucka; Miroslav Vetrik; Sergey K. Filippov; David Vetvicka; Hana Macková; Göran Karlsson; Katarina Edwards; Blanka Rihova; Karel Ulbrich

Novel polymer micelles, prepared by self-assembling thermoresponsive poly(N-isopropylacrylamide)-graft-poly[N-(2-hydroxypropyl)methacrylamide] copolymers with hydrolytically degradable N-glycosylamine groups between the polymer blocks are proposed for delivery of diagnostic and therapeutic radionuclides into solid tumors. The micelles are formed by fast heating of an aqueous solution of the copolymer to 37 degrees C. They have a hydrodynamic diameter of 128 nm (measured using dynamic light scattering) and slowly degrade during incubation in aqueous buffer at pH = 7.4. Labeling with both (131)I and (90)Y proceeds with high yields (>85%). The unlabeled polymers are not cytotoxic for any of the tested murine and human cell lines.


Journal of Agricultural and Food Chemistry | 2009

Elicitation of pharmacologically active substances in an intact medical plant.

Stanislav Kuzel; Jan Vydra; Jan Triska; Nadezda Vrchotova; Martin Hruby; Petr Cigler

The quality of medical plants used for the production of galenics or pharmacologically useful compounds is usually assessed by the content of biologically active compounds. Because most of these plants are grown in fields, this study focused on stimulation of active compounds by in vivo elicitation. Foliar application of elicitors on the immunostimulating medical plant purple coneflower ( Echinacea purpurea L. Moench.) grown on soil was used to increase the content of biologically active phenolics. Natural plant stress mediators and their derivatives (acetylsalicylic acid, salicylic acid, and methyl salicylate) as well as newly introduced biocompatible metal elicitor [titanium(IV) ascorbate] were chosen as active components of foliar sprays. A tremendous increase of phenolics (up to 10 times compared to control) and stimulation of the biomass yield were achieved. Tuning of organ specificity by modulation of the concentration of elicitor was also observed. This methodology represents a convenient alternative to cell suspension or hydroponic cultures being applicable in wide agricultural practice.


Molecular Pharmaceutics | 2014

Structural Diversity of Solid Dispersions of Acetylsalicylic Acid As Seen by Solid-State NMR

Olivia Policianova; Jiri Brus; Martin Hruby; Martina Urbanova; Alexander Zhigunov; Jana Kredatusová; Libor Kobera

Solid dispersions of active pharmaceutical ingredients are of increasing interest due to their versatile use. In the present study polyvinylpyrrolidone (PVP), poly[N-(2-hydroxypropyl)-metacrylamide] (pHPMA), poly(2-ethyl-2-oxazoline) (PEOx), and polyethylene glycol (PEG), each in three Mw, were used to demonstrate structural diversity of solid dispersions. Acetylsalicylic acid (ASA) was used as a model drug. Four distinct types of the solid dispersions of ASA were created using a freeze-drying method: (i) crystalline solid dispersions containing nanocrystalline ASA in a crystalline PEG matrix; (ii) amorphous glass suspensions with large ASA crystallites embedded in amorphous pHPMA; (iii) solid solutions with molecularly dispersed ASA in rigid amorphous PVP; and (iv) nanoheterogeneous solid solutions/suspensions containing nanosized ASA clusters dispersed in a semiflexible matrix of PEOx. The obtained structural data confirmed that the type of solid dispersion can be primarily controlled by the chemical constitutions of the applied polymers, while the molecular weight of the polymers had no detectable impact. The molecular structure of the prepared dispersions was characterized using solid-state NMR, wide-angle X-ray scattering (WAXS), and differential scanning calorimetry (DSC). By applying various (1)H-(13)C and (1)H-(1)H correlation experiments combined with T1((1)H) and T1ρ((1)H) relaxation data, the extent of the molecular mixing was determined over a wide range of distances, from intimate intermolecular contacts (0.1-0.5 nm) up to the phase-separated nanodomains reaching ca. 500 nm. Hydrogen-bond interactions between ASA and polymers were probed by the analysis of (13)C and (15)N CP/MAS NMR spectra combined with the measurements of (1)H-(15)N dipolar profiles. Overall potentialities and limitations of individual experimental techniques were thoroughly evaluated.


Biological Trace Element Research | 2003

Mechanism of physiological effects of titanium leaf sprays on plants grown on soil.

Stanislav Kuzel; Martin Hruby; Petr Cigler; Pavel Tlustoš; Phu Nguyen Van

Titanium (Ti) has significant biological effects on plants, being beneficial at low and toxic at higher concentrations. From results of our hydroponical experiment with oats, we have recently proposed that the effect called hormesis is the mechanism of Ti action in plants. Here, we present the experiment with oats (Avena sativa L. cv. Zlat’ák) grown on soil where Ti was applied using leaf sprays. Two different soils, three different concentrations of Ti(IV) citrate spray solution (0, 20, and 50 mg Ti/kg), and three different Mg concentrations in each soil were tested. Some physiological parameters (dry and raw weights, top heights, chlorophyll content) and element contents (Mg, Fe, Zn, Mn) were determined. Ti showed considerable effects on all physiological parameters and the element’s contents were determined. Differences between the two different soil types used was only in the strength of the effect of Ti; the trends remained unchanged. Generally, the effect of Ti is considerably weaker if Ti is applied on leaves than if being added to the nutrient solution. Thus, we confirm here that the action of Ti on plants could be explained by the hormesis effect.


European Journal of Pharmaceutical Sciences | 2011

Thermoresponsive polymeric radionuclide delivery system—An injectable brachytherapy

Martin Hruby; Pavla Pouckova; Marie Zadinova; Jan Kucka; Ondrej Lebeda

Brachytherapy is of increasing popularity in clinical oncology for the local therapy of solid tumors due to high radiation doses delivered to malignant tissue while keeping the whole-body radiation burden low. Pronounced dose-dependent tumor growth reduction was achieved by single dose of injectable intratumoral brachytherapy with iodine-131-labeled thermoresponsive polymer [poly(N-isopropyl acrylamide)] in murine xenograft model (PC3 human prostate adenocarcinoma). The two doses of radionuclide were used, 2 MBq/mouse and 25 MBq/mouse. The higher dose caused gradual tumor volume reduction and 2 of 6 mice from this group were cured. The lower dose caused tumor growth retardation only. In both cases there were no signs of inflammation. The effects of both doses were statistically significant compared to untreated controls. Such injectable system should keep advantages of brachytherapy while making system administration easier and less invasive (injection instead of implantation), patient-tailored (splitting of doses into several depoes) and bioerodable.


Journal of Separation Science | 2014

Silver‐coated monolithic columns for separation in radiopharmaceutical applications

Ondrej Sedlacek; Jan Kucka; Frantisek Svec; Martin Hruby

In this study, we demonstrate the preparation of a macroporous monolithic column containing anchored silver nanoparticles and its use for the elimination of excess radioiodine from the radiolabeled pharmaceutical. The poly(glycidyl methacrylate-co-ethylene dimethacrylate) monolith was first functionalized with cystamine and the free thiol groups liberated by reaction with borohydride. In-house-prepared silver nanoparticles were then attached by interaction with the surface thiols. The deiodization process was demonstrated with the commonly used radiopharmaceutical m-iodobenzylguanidine labeled with radionuclide iodine-125.


Bioconjugate Chemistry | 2011

Ellipticine-aimed polymer-conjugated auger electron emitter: multistage organelle targeting approach.

Ondrej Sedlacek; Martin Hruby; Martin Studenovsky; Jan Kucka; David Vetvicka; Lubomir Kovar; Blanka Rihova; Karel Ulbrich

Radioactive decay of some radionuclides produces a shower of Auger electrons, potent ionizing radiation within a very short range in living tissue (typically ca. 100 nm). Therefore, they must be brought to DNA-containing cell compartments and preferentially directly to DNA to be fully biologically effective. They may be used for a triple-targeting approach (first targeting, polymer-based system targeting into tumor tissue due to EPR effect; second targeting, pH-controlled release of intercalator-bound Auger electron emitter in slightly acidic tumor tissue or endosome; third targeting, into DNA in cell nucleus by the intercalator) minimizing radiation burden of healthy tissues. We describe a first system of this type, an ellipticine derivative-bound iodine-125 attached to hydrazide moieties containing poly[N-(2-hydroxypropyl)methacrylamide]. The system is stable at pH 7.4 (0% intercalator released after 24 h incubation), while iodine-containing biologically active intercalator is released upon decrease of pH (25% intercalator released after 24 h incubation at pH 5.0-model of late endosomes). Both 2-N-(2-oxobutyl)-9-iodoellipticinium bromide and the noniodinated 2-N-(2-oxobutyl)ellipticinium bromide are potent intercalators, as proven by direct titration with DNA and ethidium displacement assay, and readily penetrate into cell nuclei, as proven by confocal microscopy. They retain chemotherapeutical antiproliferative properties of ellipticine against Raji, EL-4, and 4T1cells with IC(50) in the range 0.27-8.8 μmol/L. Polymer conjugate of 2-N-(2-oxobutyl)-9-iodoellipticinium bromide is internalized into endosomes, releases active drug, possesses cytotoxic activity, and the drug accumulates in cell nuclei.

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Petr Stepanek

Academy of Sciences of the Czech Republic

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Jan Kucka

Academy of Sciences of the Czech Republic

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Sergey K. Filippov

Academy of Sciences of the Czech Republic

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Miroslav Vetrik

Academy of Sciences of the Czech Republic

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Ondrej Sedlacek

Academy of Sciences of the Czech Republic

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Hana Macková

Academy of Sciences of the Czech Republic

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Karel Ulbrich

Academy of Sciences of the Czech Republic

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Petr Cigler

Academy of Sciences of the Czech Republic

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Jiri Brus

Academy of Sciences of the Czech Republic

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Miroslav Šlouf

Academy of Sciences of the Czech Republic

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