36 results on '"Ciepluch K"'
Search Results
2. Coagulation profile in patients with H1N1 influenza A infection undergoing treatment for haematological malignancies: PB 3.66–6
- Author
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Rupa-Matysek, J, Gil, L, Wojtasinska, E, Zajdel, K, Ciepluch, K, and Komarnicki, M
- Published
- 2013
3. Coagulation profile in patients with acute leukaemia receiving myeloablative or reduced-intensity conditioning regimens for allogeneic hematopoietic stem cell transplantation: PB 3.31–2
- Author
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Rupa-Matysek, J, Czyz, A, Gil, L, Wojtasinska, E, Zajdel, K, Ciepluch, K, and Komarnicki, M
- Published
- 2013
4. Biophysical Characterization of Glycodendrimers As Nano-carriers for HIV Peptides
- Author
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Ionov, M., primary, Ciepluch, K., additional, Moreno, B., additional, Appelhans, D., additional, Sanchez-Nieves, J., additional, Gomez, R., additional, de la Mata, F., additional, Munoz-Fernandez, M., additional, and Bryszewska, M., additional
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- 2013
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5. The biodistribution of maltotriose modified poly(propylene imine) (PPI) dendrimers conjugated with fluorescein—proofs of crossing blood–brain–barrier
- Author
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Janaszewska, A., primary, Ziemba, B., additional, Ciepluch, K., additional, Appelhans, D., additional, Voit, B., additional, Klajnert, B., additional, and Bryszewska, M., additional
- Published
- 2012
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6. Ocena zaburzeń krzepnięcia u pacjentów zakażonych wirusem grypy typu A/H1N1 podczas leczenia chorób rozrostowych układu krwiotwórczego
- Author
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Rupa-Matysek, J., Gil, L., Wojtasińska, E., Zajdel, K., Ciepłuch, K., and Komarnicki, M.
- Published
- 2013
- Full Text
- View/download PDF
7. Analiza występowania wrodzonego niedoboru antytrombiny w grupie pacjentek z niepowodzeniami ciąży
- Author
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Wojtasińska, E., Rupa-Matysek, J., Ciepłuch, K., Zajdel, K., Michalak, M., and Komarnicki, M.
- Published
- 2013
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8. Ocena układu białka C u dorosłych pacjentów poddanych allotransplantacji komórek krwiotwórczych z powodu ostrych białaczek
- Author
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Rupa-Matysek, J., Czyż, A., Gil, L., Wojtasińska, E., Zajdel, K., Ciepłuch, K., Łojko-Dankowska, A., and Komarnicki, M.
- Published
- 2013
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9. Ocena zaburzeń krzepnięcia metodą tromboelastometrii u pacjentów poddanych wysokodawkowej chemioterapii wspomaganej przetoczeniem allogenicznych komórek krwiotwórczych
- Author
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Rupa-Matysek, J., Gil, L., Wojtasińska, E., Zajdel, K., Ciepłuch, K., and Komarnicki, M.
- Published
- 2013
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10. Wpływ rozpoznania trombofilii złożonej na ryzyko nawrotu żylnej choroby zakrzepowo-zatorowej
- Author
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Rupa-Matysek, J., Wojtasińska, E., Zajdel, K., Ciepłuch, K., and Komarnicki, M.
- Published
- 2013
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11. Średnia objętość płytek krwi (MPV) jako marker nawrotu zakrzepicy u chorych z pierwotnym zespołem antyfosfolipidowym
- Author
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Rupa-Matysek, J., Gil, L., Wojtasińska, E., Zajdel, K., Ciepłuch, K., Lewandowska, M., and Komarnicki, M.
- Published
- 2013
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12. UNDERSTANDING THE PEGYLATION EFFECT ON BIOLOGICAL PROPERTIES OF PROTEINS AND DENDRITIC NANOPARTICLES.
- Author
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Ciepluch, K., Kuc-Ciepluch, D., Barrios-Gumiel, A., Quintana, S., Sánchez-Nieves, J., de la Mata, F. J., Bryszewska, M., Biehl, R., and Arabski, M.
- Subjects
- *
NANOPARTICLES , *DENDRIMERS , *THERMODYNAMIC control - Published
- 2019
13. Endolysin CHAP domain-carbosilane metallodendrimer complexes with triple action on Gram-negative bacteria: Membrane destabilization, reactive oxygen species production and peptidoglycan degradation.
- Author
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Lach K, Skrzyniarz K, Takvor-Mena S, Łysek-Gładysińska M, Furmańczyk P, Barrios-Gumiel O, Sanchez-Nieves J, and Ciepluch K
- Abstract
Bacterial resistance to antibiotics is a significant challenge that is associated with increased morbidity and mortality. Gram-negative bacteria are particularly problematic due to an outer membrane (OM). Current alternatives to antibiotics include antimicrobial peptides or proteins and multifunctional systems such as dendrimers. Antimicrobial proteins such as lysins can degrade the bacterial cell wall, whereas dendrimers can permeabilize the OM, enhancing the activity of endolysins against gram-negative bacteria. In this study, we present a three-stage action of endolysin combined with two different carbosilane (CBS) silver metallodendrimers, in which the periphery is modified with N-heterocyclic carbene (NHC) ligands coordinating a silver atom. The different NHC ligands contained hydrophobic methyl or N-donor pyridyl moieties. The effects of these endolysin/dendrimer combinations are based on OM permeabilization, peptidoglycan degradation, and reactive oxygen species production. The results showed that CBS possess a permeabilization effect (first action), significantly reduced bacterial growth at higher concentrations alone and in the presence of endolysin, increased ROS production (second action), and led to bacterial cell damage (third action). The complex formed between the CHAP domain of endolysin and a CBS silver metallodendrimer, with a triple mechanism of action, may represent an excellent alternative to other antimicrobials with only one resistance mechanism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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14. Molecular mechanism of action of imidazolium carbosilane dendrimers on the outer bacterial membrane - From membrane damage to permeability to antimicrobial endolysin.
- Author
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Skrzyniarz K, Takvor-Mena S, Lach K, Łysek-Gładysińska M, Barrios-Gumiel Ó, Cano J, and Ciepluch K
- Subjects
- Anti-Bacterial Agents pharmacology, Gram-Negative Bacteria, Permeability, Lipids, Microbial Sensitivity Tests, Dendrimers pharmacology, Endopeptidases, Silanes
- Abstract
The outer bacterial membrane of drug-resistant bacteria is a significant barrier to many antimicrobials. Therefore, the development of new antibacterials primarily focuses on damaging the outer bacterial membrane of Gram-negative bacteria. Among many membrane-disrupting substances, the most promising are cationic dendritic systems. However, the mode of action may vary among different strains due to variations in the lipid compositions of the membrane. Here, we investigated the interaction of two types of cationic imidazolium carbosilane dendrimers: one with a single cationic group (methyl imidazolium) and the other with the same cationic group but attached to a functional group (a pendant pyridyl moiety), capable of establishing interactions with membranes through H-bonding or ion-dipole electrostatic interactions. We used different models of the outer membrane of Gram-negative bacteria - Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. Additionally, we assessed the combined effect of the dendrimers and the antibacterial endolysin on P. aeruginosa. Our results show that the mechanism of action depends on the type of dendrimer and the lipid composition of the membrane. We also demonstrate that the alteration of membrane fluidity and permeability to endolysin by the methyl imidazolium and pyridyl imidazolium dendrimers may play a more significant role in antimicrobial activity compared to membrane damage caused by positively charged dendrimers., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Karol Ciepluch reports financial support was provided by National Science Centre Poland. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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15. Dendronized Ag/Au Nanomats: Antimicrobial Scaffold for Wound Healing Bandages.
- Author
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Lasak M, Nirwan VP, Kuc-Ciepluch D, Lysek-Gladysinska M, Javier de la Mata F, Gomez R, Fahmi A, and Ciepluch K
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- Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents chemistry, Tissue Scaffolds chemistry, Dendrimers chemistry, Dendrimers pharmacology, Animals, Mice, Nanofibers chemistry, Humans, Anti-Infective Agents pharmacology, Anti-Infective Agents chemistry, Polyesters chemistry, Polyesters pharmacology, Silver chemistry, Silver pharmacology, Wound Healing drug effects, Gold chemistry, Gold pharmacology, Pseudomonas aeruginosa drug effects, Metal Nanoparticles chemistry, Bandages
- Abstract
Electrospun polymer nanofibers, due to high surface area-to-volume ratio, high porosity, good mechanical strength, and ease of functionalization, appear as promising multifunctional materials for biomedical applications. Thanks to their unidirectional structure, imitating the extracellular matrix (ECM), they can be used as scaffolds for cell adhesion and proliferation. In addition, the incorporation of active groups inside nanofiber can give properties for bactericides. The proposed nanomats incorporate nanoparticles templated within the electrospun nanofibers that prevent infections and stimulate tissue regeneration. The generated hybrid electrospun nanofibers are composed of a copolymer of L-lactide-block-ε-caprolactone (PL-b-CL), 70:30, blended with homopolymer polyvinylpyrrolidone (PVP) and gold (Au) nanoparticles. A low cytotoxicity and slightly increased immunoreactivity, stimulated by the nanomat, are observed. Moreover, the decoration of the hybrid nanomat with dendronized silver nanoparticles (Dend-Ag) improves their antibacterial activity against antibiotic-resistant Pseudomonas aeruginosa. The use of Dend-Ag for decorating offers several functional effects; namely, it enhances the antibacterial properties of the produced nanomats and induces a significant increase within macrophages' cytotoxicity. The unidirectional nanostructures of the generated hybrid nanomats demonstrate unique collective physio-chemical and biological properties suitable for a wide range of biomedical applications. Here, the antibacterial properties facilitate an optimal environment, contributing to accelerated wound healing., (© 2024 Wiley‐VCH GmbH.)
- Published
- 2024
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16. Dendritic systems for bacterial outer membrane disruption as a method of overcoming bacterial multidrug resistance.
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Skrzyniarz K, Kuc-Ciepluch D, Lasak M, Arabski M, Sanchez-Nieves J, and Ciepluch K
- Subjects
- Drug Resistance, Multiple, Gram-Negative Bacteria, Microbial Sensitivity Tests, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents chemistry, Bacterial Outer Membrane
- Abstract
The alarming rise of multi-drug resistant microorganisms has increased the need for new approaches through the development of innovative agents that are capable of attaching to the outer layers of bacteria and causing permanent damage by penetrating the bacterial outer membrane. The permeability (disruption) of the outer membrane of Gram-negative bacteria is now considered to be one of the main ways to overcome multidrug resistance in bacteria. Natural and synthetic permeabilizers such as AMPs and dendritic systems seem promising. However, due to their advantages in terms of biocompatibility, antimicrobial capacity, and wide possibilities for modification and synthesis, highly branched polymers and dendritic systems have gained much more interest in recent years. Various forms of arrangement, and structure of the skeleton, give dendritic systems versatile applications, especially the possibility of attaching other ligands to their surface. This review will focus on the mechanisms used by different types of dendritic polymers, and their complexes with macromolecules to enhance their antimicrobial effect, and to permeabilize the bacterial outer membrane. In addition, future challenges and potential prospects are illustrated in the hope of accelerating the advancement of nanomedicine in the fight against resistant pathogens.
- Published
- 2023
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17. Mechanistic insight of lysozyme transport through the outer bacteria membrane with dendronized silver nanoparticles for peptidoglycan degradation.
- Author
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Skrzyniarz K, Sanchez-Nieves J, de la Mata FJ, Łysek-Gładysińska M, Lach K, and Ciepluch K
- Subjects
- Peptidoglycan, Silver, Anti-Bacterial Agents pharmacology, Bacteria metabolism, Polyethylene Glycols, Muramidase metabolism, Metal Nanoparticles
- Abstract
Drug resistance has become a global problem, prompting the entire scientific world to seek alternative methods of dealing with resistant pathogens. Among the many alternatives to antibiotics, two appear to be the most promising: membrane permeabilizers and enzymes that destroy bacterial cell walls. Therefore, in this study, we provide insight into the mechanism of lysozyme transport strategies using two types of carbosilane dendronized silver nanoparticles (DendAgNPs), non-polyethylene glycol (PEG)-modified (DendAgNPs) and PEGylated (PEG-DendAgNPs), for outer membrane permeabilization and peptidoglycan degradation. Remarkably, studies have shown that DendAgNPs can build up on the surface of a bacterial cell, destroying the outer membrane, and thereby allowing lysozymes to penetrate inside the bacteria and destroy the cell wall. PEG-DendAgNPs, on the other hand, have a completely different mechanism of action. PEG chains containing a complex lysozyme resulted in bacterial aggregation and an increase in the local enzyme concentration near the bacterial membrane, thereby inhibiting bacterial growth. This is due to the accumulation of the enzyme in one place on the surface of the bacteria and penetration into it through slight damage of the membrane due to interactions of NPs with the membrane. The results of this study will help propel more effective antimicrobial protein nanocarriers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
- Published
- 2023
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18. Overview of mechanism and consequences of endothelial leakiness caused by metal and polymeric nanoparticles.
- Author
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Lasak M and Ciepluch K
- Abstract
Nanoparticles (NPs) exhibit unique physicochemical properties that enable them to overcome biological barriers and to be considered one of the best materials with anticancer properties. Most of the administered NPs that end up in the bloodstream interact with the endothelial layer. The interaction of the NPs with the endothelium widens the existing gaps or induces new ones in the monolayer of vascular endothelial cells, thus increasing the access to the target sites in the organism. This type of interaction can lead to NP-modulated endothelial leakiness (NanoEL). The most important factors determining NanoEL are the physicochemical properties of the NPs. NP-modulated endothelial leakiness can lead to the discovery of new therapeutic targets and strategies to improve drug delivery through controlling and regulating NanoEL. Nevertheless, the NanoEL mechanism also carries some limitations that result from an incomplete understanding of NP metabolism and toxicity, and the possibility of their participation in the unintended bidirectional vascular permeability, which may contribute to the formation of cancer metastases. In this review we are focusing on the effect of metal and polymeric NPs on mechanism and degree of induction of NanoEL, as well as on the benefits and risks of using NPs that induce endothelial leakiness., (Copyright © 2023, Lasak and Ciepluch.)
- Published
- 2023
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19. Hybrid Nanomat: Copolymer Template CdSe Quantum Dots In Situ Stabilized and Immobilized within Nanofiber Matrix.
- Author
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Nirwan VP, Lasak M, Ciepluch K, and Fahmi A
- Abstract
Fabrication and characterization of hybrid nanomats containing quantum dots can play a prominent role in the development of advanced biosensors and bio-based semiconductors. Owing to their size-dependent properties and controlled nanostructures, quantum dots (QDs) exhibit distinct optical and electronic characteristics. However, QDs include heavy metals and often require stabilizing agents which are toxic for biological applications. Here, to mitigate the use of toxic ligands, cadmium selenide quantum dots (CdSe QDs) were synthesized in situ with polyvinylpyrrolidone (PVP) at room temperature. The addition of PVP polymer provided size regulation, stability, and control over size distribution of CdSe QDs. The characterization of the optical properties of the CdSe QDs was performed using fluorescence and ultraviolet-visible (UV-Vis) spectroscopy. CdSe QDs exhibited a typical absorbance peak at 280 nm and a photoluminescence emission peak at 580 nm. Transmission electron microscopy (TEM) micrographs demonstrated that CdSe QDs having an average size of 6 ± 4 nm were obtained via wet chemistry method. CdSe QDs were immobilized in a blend of PVP and poly(L-lactide-co-ε-caprolactone) (PL-b-CL) copolymer that was electrospun to produce nanofibers. Scanning electron microscopy (SEM), thermal analyses and attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) were used to characterize properties of fabricated nanofibers. Both pristine and hybrid nanofibers possessed cylindrical geometry and rough surface features, facilitating increased surface area. Infrared absorption spectra showed a slight shift in absorbance peaks due to interaction of PVP-coated CdSe QDs and nanofiber matrix. The presence of CdSe QDs influenced the fiber diameter and their thermal stability. Further, in vitro biological analyses of hybrid nanofibers showed promising antibacterial effect and decline in cancer cell viability. This study offers a simple approach to obtain hybrid nanomats immobilized with size-controlled PVP-coated CdSe QDs, which have potential applications as biosensors and antibacterial and anticancer cell agents., Competing Interests: The authors declare no conflicts of interest.
- Published
- 2023
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20. The effect of surface modification of dendronized gold nanoparticles on activation and release of pyroptosis-inducing pro-inflammatory cytokines in presence of bacterial lipopolysaccharide in monocytes.
- Author
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Kuc-Ciepluch D, Gorzkiewicz M, Pędziwiatr-Werbicka E, Barrios-Gumiel A, Lasak M, Mariak A, Sztandera K, Gomez R, de la Mata FJ, Lankoff A, Klajnert-Maculewicz B, Bryszewska M, Arabski M, and Ciepluch K
- Subjects
- Cytokines metabolism, Gold metabolism, Gold pharmacology, Interleukin-1beta, Monocytes, Pyroptosis, Lipopolysaccharides pharmacology, Metal Nanoparticles
- Abstract
Biomedical applications of gold nanoparticles (AuNPs) may be limited by their toxicological effects. Although surface-modified AuNPs can induce apoptosis, less is known about whether they can induce other types of cell death. Pyroptosis, an inflammatory type of programmed cell death, can be induced in immune cells, especially macrophages, by bacterial endotoxins. Therefore, in this study, dendronized AuNPs were combined with bacterial lipopolysaccharides (LPSs) as the main stimulators of pro-inflammatory responses to test the induction of pyroptosis in THP-1 myeloid cell line. These AuNPs induced caspase-1 activity (3-4 times more compared to control) and enhanced the release of interleukin (IL)-18 and IL-1β without inducing gasdermin D cleavage and related pore formation. The production of pro-inflammatory cytokines occurred mainly visible during LPS treatment, although their secretion was observed only after administration of dendronized AuNPs (release of IL-1β to supernatant up to 80 pg/mL). These findings suggest that dendronized AuNPs can induce pyroptosis-like inflammatory mechanisms and that these mechanisms are enhanced in the presence of bacterial LPS. The intensity of this effect was dependent on AuNP surface modification. These results shed new light on the cytotoxicity of metal NPs, including immune responses, indicating that surface modifications play crucial roles in their nanotoxicological effects., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2022
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21. The Antibacterial Effect of PEGylated Carbosilane Dendrimers on P. aeruginosa Alone and in Combination with Phage-Derived Endolysin.
- Author
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Quintana-Sanchez S, Gómez-Casanova N, Sánchez-Nieves J, Gómez R, Rachuna J, Wąsik S, Semaniak J, Maciejewska B, Drulis-Kawa Z, Ciepluch K, Mata FJ, and Arabski M
- Subjects
- Anti-Bacterial Agents chemistry, Bacteriophages metabolism, Biofilms drug effects, Dendrimers, Drug Compounding, Drug Synergism, Interferometry, Microbial Sensitivity Tests, Microbial Viability drug effects, Microscopy, Fluorescence, Plankton drug effects, Pseudomonas aeruginosa drug effects, Silanes chemistry, Anti-Bacterial Agents pharmacology, Endopeptidases pharmacology, Polyethylene Glycols chemistry, Pseudomonas aeruginosa growth & development, Silanes pharmacology
- Abstract
The search for new microbicide compounds is of an urgent need, especially against difficult-to-eradicate biofilm-forming bacteria. One attractive option is the application of cationic multivalent dendrimers as antibacterials and also as carriers of active molecules. These compounds require an adequate hydrophilic/hydrophobic structural balance to maximize the effect. Herein, we evaluated the antimicrobial activity of cationic carbosilane (CBS) dendrimers unmodified or modified with polyethylene glycol (PEG) units, against planktonic and biofilm-forming P. aeruginosa culture. Our study revealed that the presence of PEG destabilized the hydrophilic/hydrophobic balance but reduced the antibacterial activity measured by microbiological cultivation methods, laser interferometry and fluorescence microscopy. On the other hand, the activity can be improved by the combination of the CBS dendrimers with endolysin, a bacteriophage-encoded peptidoglycan hydrolase. This enzyme applied in the absence of the cationic CBS dendrimers is ineffective against Gram-negative bacteria because of the protective outer membrane shield. However, the endolysin-CBS dendrimer mixture enables the penetration through the membrane and then deterioration of the peptidoglycan layer, providing a synergic antimicrobial effect.
- Published
- 2022
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22. Spectroscopic and Small-angle X-ray scattering analysis of binding between Copper(II) -1-allylimidazole complex, a potential anti-tumor agent, and bovine serum albumin.
- Author
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Gałczyńska K, Ciepluch K, Kurdziel K, Biehl R, and Arabski M
- Subjects
- Animals, Binding Sites, Cattle, Circular Dichroism, Molecular Structure, Scattering, Small Angle, Spectrometry, Fluorescence, X-Ray Diffraction, Antineoplastic Agents chemistry, Coordination Complexes chemistry, Copper chemistry, Imidazoles chemistry, Serum Albumin, Bovine chemistry
- Abstract
Interactions between transport proteins and compounds with therapeutic potential are pharmacologically important. In this study, using fluorescence, circular dichroism (CD), and small-angle X-ray Scattering (SAXS), we investigated the interaction between bovine serum albumin (BSA) and a copper(II)-1-allylimidazole complex with potential anti-cancer properties. The results revealed dynamic fluorescence quenching of the model carrier protein BSA by the copper(II) complex. The enthalpy change (ΔH), free energy (ΔG), and entropy change (ΔS) were calculated to be 108 kJ/mol, -16.47 kJ/mol, and 419 J/mol K, respectively, according to the Van't Hoff equation. The reaction was an endothermic and spontaneous process, and hydrophobic interactions played a major role in binding. The results indicate a much lower affinity (K
b ∼ 102 -103 ) for the metal complex compared with similar compounds (Kb ∼ 103 -105 ). CD showed that the studied copper(II) complex does not change the secondary structure of the protein, while SAXS showed that the this compound may attach to the protein surface and stimulate interactions between proteins. The results suggest that the copper(II) complex with 1-allylimidazole binds weakly to BSA, leading to aggregation of albumin in solution, thereby altering its pharmacokinetic properties. The findings are pertinent to drug design., (Copyright © 2021 Elsevier Inc. All rights reserved.)- Published
- 2021
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23. Coralyne Radiosensitizes A549 Cells by Upregulation of CDKN1A Expression to Attenuate Radiation Induced G2/M Block of the Cell Cycle.
- Author
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Węgierek-Ciuk A, Arabski M, Ciepluch K, Brzóska K, Lisowska H, Czerwińska M, Stępkowski T, Lis K, and Lankoff A
- Subjects
- A549 Cells, Actin Cytoskeleton drug effects, Actin Cytoskeleton radiation effects, Cell Survival drug effects, Cell Survival radiation effects, Cyclin-Dependent Kinase Inhibitor p21 metabolism, Dose-Response Relationship, Drug, Dose-Response Relationship, Radiation, G2 Phase Cell Cycle Checkpoints radiation effects, Humans, Microscopy, Confocal, Radiation, Ionizing, Radiation-Sensitizing Agents pharmacology, Berberine Alkaloids pharmacology, Cyclin-Dependent Kinase Inhibitor p21 genetics, G2 Phase Cell Cycle Checkpoints drug effects, Gene Expression Regulation, Neoplastic drug effects, Up-Regulation drug effects
- Abstract
Coralyne is a synthetic analog of berberine related to protoberberine-isoquinoline alkaloids. Isoquinoline derivatives and analogs are renowned as potent radiosensitizers with potential medical application. In the present study, we investigated the effect of coralyne on the cell death, cytoskeletal changes and cell cycle progression of irradiated A549 cells. A clonogenic assay revealed that coralyne pretreatment decreased the viability of A549 cells in a time- and dose-dependent manner. Moreover, exposure to coralyne and ionizing radiation (IR) markedly altered the filamentous actin cytoskeletal architecture and integrin-β binding sites of A549 cells. Treatment with 1-25 µM coralyne in combination with 2 Gy of IR significantly reduced the percentage of cells in G2/M phase compared with 2 Gy IR alone. These results indicate that coralyne is a potent radiosensitizing agent that may find an application in medicine.
- Published
- 2021
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24. Experimental and Theoretical Analysis of Metal Complex Diffusion through Cell Monolayer.
- Author
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Gałczyńska K, Rachuna J, Ciepluch K, Kowalska M, Wąsik S, Kosztołowicz T, Lewandowska KD, Semaniak J, Kurdziel K, and Arabski M
- Abstract
The study of drugs diffusion through different biological membranes constitutes an essential step in the development of new pharmaceuticals. In this study, the method based on the monolayer cell culture of CHO-K1 cells has been developed in order to emulate the epithelial cells barrier in permeability studies by laser interferometry. Laser interferometry was employed for the experimental analysis of nickel(II) and cobalt(II) complexes with 1-allylimidazole or their chlorides' diffusion through eukaryotic cell monolayers. The amount (mol) of nickel(II) and cobalt(II) chlorides transported through the monolayer was greater than that of metals complexed with 1-allylimidazole by 4.34-fold and 1.45-fold, respectively, after 60 min. Thus, laser interferometry can be used for the quantitative analysis of the transport of compounds through eukaryotic cell monolayers, and the resulting parameters can be used to formulate a mathematical description of this process.
- Published
- 2021
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25. Poly(propylene imine) dendrimers can bind to PEGylated albumin at PEG and albumin surface: Biophysical examination of a PEGylated platform to transport cationic dendritic nanoparticles.
- Author
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Ciepluch K, Biehl R, Bryszewska M, and Arabski M
- Subjects
- Animals, Biological Transport, Cattle, Dendrimers metabolism, Drug Delivery Systems methods, Nanoparticles metabolism, Polyethylene Glycols metabolism, Polypropylenes metabolism, Scattering, Small Angle, Serum Albumin, Bovine metabolism, Surface Properties, X-Ray Diffraction, Dendrimers chemistry, Nanoparticles chemistry, Polyethylene Glycols chemistry, Polypropylenes chemistry, Serum Albumin, Bovine chemistry
- Abstract
Cationic dendrimers are considered one of the best drug transporters in the body. However, in order to improve their biocompatibility, modification of them is required to reduce toxicity. In this way, many dendrimers may lose their original properties, for example, anticancer. To improve biocompatibility of dendrimers, it is possible to complex them with albumin, as is done very often in drug delivery. However, the interaction of dendrimers with albumin can lead to protein structure disruption or no complexation at all. Therefore, the investigation of the interaction between cationic poly-(propylene imine) dendrimers and polyethylene glycol (PEG)-albumin by fluorescence, circular dichroism, small angle X-ray scattering (SAXS), and transmission electron microscopy was carried out. Results show that cationic dendrimers bind to PEGylated albumin at PEG and albumin surfaces. The obtained results for 5k-PEG indicate a preferential binding of the dendrimers to PEG. For 20k-PEG binding of dendrimers to PEG and protein could induce a collapse of the PEG chain onto the protein surface. This opens up new possibilities to the use of PEGylated albumin as a platform to carry dendrimers without changing the albumin structure and improve the pharmacokinetic properties of dendrimers without further modification., (© 2020 Wiley Periodicals, Inc.)
- Published
- 2020
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26. Effect of PEGylation on the biological properties of cationic carbosilane dendronized gold nanoparticles.
- Author
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Barrios-Gumiel A, Sánchez-Nieves J, Pedziwiatr-Werbicka E, Abashkin V, Shcharbina N, Shcharbin D, Glińska S, Ciepluch K, Kuc-Ciepluch D, Lach D, Bryszewska M, Gómez R, and de la Mata FJ
- Subjects
- Cations chemistry, Cell Survival drug effects, Chemistry Techniques, Synthetic methods, Chemistry, Pharmaceutical methods, Dendrimers chemistry, Drug Carriers chemistry, Dynamic Light Scattering, Erythrocytes drug effects, Gold chemistry, HeLa Cells, Humans, Leukocytes, Mononuclear, Magnetic Resonance Spectroscopy, Metal Nanoparticles chemistry, Metal Nanoparticles ultrastructure, Microscopy, Electron, Transmission, Platelet Aggregation drug effects, Polyethylene Glycols chemistry, Silanes chemistry, Toxicity Tests, Dendrimers toxicity, Drug Carriers toxicity, Gold toxicity, Metal Nanoparticles toxicity, Silanes toxicity
- Abstract
Heterofunctionalized gold nanoparticles (AuNPs) were obtained in a one pot reaction of gold precursor with cationic carbosilane dendrons (first to third generations, 1-3G) and (polyethylene)glycol (PEG) ligands in the presence of a reducing agent. The final dendron/PEG proportion on AuNPs depends on the initial dendron/PEG ratio (3/1, 1/1, 1/3) and dendron generation. AuNPs were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), ultraviolet spectroscopy (UV-VIS), thermogravimetric analysis (TGA), nuclear magnetic resonance (
1 H NMR) and zeta potential (ZP). Several assays have been carried out to determine the relevance of PEG/dendron ratio and dendron generation in the biomedical properties of PEGylated AuNPs and the results have been compared with those obtained for non-PEGylated AuNPs. Finally, analyses of PEG recognition by anti-PEG antibodies were carried out. In general, haemolysis, platelet aggregation and toxicity were reduced after PEGylation of AuNPs, the effect being dependent on dendron generation and dendron/PEG ratio. Dendron generation determines the exposure of PEG ligand and the interaction of this ligand with AuNPs environment. On the other hand, increasing PEG proportion diminishes toxicity but also favors interaction with antibodies., (Copyright © 2019 Elsevier B.V. All rights reserved.)- Published
- 2020
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27. Dendronized Silver Nanoparticles as Bacterial Membrane Permeabilizers and Their Interactions With P. aeruginosa Lipopolysaccharides, Lysozymes, and Phage-Derived Endolysins.
- Author
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Ciepluch K, Skrzyniarz K, Barrios-Gumiel A, Quintana S, Sánchez-Nieves J, de la Mata FJ, Maciejewska B, Drulis-Kawa Z, and Arabski M
- Abstract
Antimicrobial proteins, like lysozymes produced by animals or bacteriophage lysins, enable the degradation of bacterial peptidoglycan (PG) and, consequently, lead to bacterial cell lysis. However, the activity of those enzymes is not satisfactory against gram-negative bacteria because of the presence of an outer membrane (OM) barrier. Lytic enzymes can therefore be combined with membrane-disrupting agents, such as dendritic silver nanoparticles. Nevertheless, a lipopolysaccharide (LPS), especially the smooth type, could be the main hindrance for highly charged nanoparticles to get direct access to the bacterial OM and to help lytic enzymes to reach their target PG. Herein, we have investigated the interactions of PEGylated carbosilane dendritic nanoparticles with P. aeruginosa 010 LPS in the presence of lysozymes and KP27 endolysin to find out the main aspects of the OM destabilization process. Our results showed that PEGylated dendronized AgNPs overcame the LPS barrier and enhanced the antibacterial effect of endolysin more efficiently than unPEGylated nanoparticles., (Copyright © 2019 Ciepluch, Skrzyniarz, Barrios-Gumiel, Quintana, Sánchez-Nieves, de la Mata, Maciejewska, Drulis-Kawa and Arabski.)
- Published
- 2019
- Full Text
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28. The influence of cationic dendrimers on antibacterial activity of phage endolysin against P. aeruginosa cells.
- Author
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Ciepluch K, Maciejewska B, Gałczyńska K, Kuc-Ciepluch D, Bryszewska M, Appelhans D, Drulis-Kawa Z, and Arabski M
- Subjects
- Anti-Bacterial Agents chemistry, Bacteriophages enzymology, Dendrimers chemistry, Drug Synergism, Endopeptidases chemistry, Klebsiella virology, Maltose analogs & derivatives, Microbial Sensitivity Tests, Protein Stability, Anti-Bacterial Agents pharmacology, Dendrimers pharmacology, Endopeptidases pharmacology, Pseudomonas aeruginosa drug effects
- Abstract
Nowadays, the researchers make a big effort to find new alternatives to overcome bacterial drug resistance. One option is the application of bacteriophage endolysins enable to degrade peptidoglycan (PG) what in consequence leads to bacterial cell lysis. In this study we examine phage KP27 endolysin mixed with poly(propyleneimine) dendrimers to evaluate an antimicrobial effect against Pseudomonas aeruginosa. Polycationic compounds destabilize bacterial outer membrane (OM) helping endolysins to gain access to PG. We found out that not only bacterial lipopolysaccharide (LPS) is the main hindrance for highly charged cationic dendrimers to disrupt OM and make endolysin reaching the target but also the dendrimer surface modification. The reduction of a positive charge and concentration in maltose poly(propyleneimine) dendrimers significantly increased an antibacterial effect of endolysin. The application of recombinant lysins against Gram-negative bacteria is one of the future therapy options, thus OM permeabilizers such as cationic dendrimers may be of high interest to be combined with PG-degrading enzymes., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
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29. Selective cytotoxicity and antifungal properties of copper(II) and cobalt(II) complexes with imidazole-4-acetate anion or 1-allylimidazole.
- Author
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Gałczyńska K, Ciepluch K, Madej Ł, Kurdziel K, Maciejewska B, Drulis-Kawa Z, Węgierek-Ciuk A, Lankoff A, and Arabski M
- Subjects
- Cell Line, Tumor, DNA chemistry, DNA metabolism, Fungi drug effects, Humans, Microbial Sensitivity Tests, Models, Molecular, Molecular Conformation, Molecular Structure, Antifungal Agents chemistry, Antifungal Agents pharmacology, Cobalt chemistry, Coordination Complexes chemistry, Coordination Complexes pharmacology, Copper chemistry, Imidazoles chemistry
- Abstract
The physicochemical properties of metal complexes determine their potential applications as antitumor agents. In this study, the antitumor properties of mononuclear cobalt(II) and copper(II) coordination compounds (stoichiometry: [Co(iaa)
2 (H2 O)2 ]·H2 O (iaa = imidazole-4-acetate anion), [Co(1-allim)6 ](NO3 )2 (1-allim = 1-allylimidazole), [Cu(iaa)2 H2 O] and [Cu(1-allim)4 (NO3 )2 ]) and their ligands have been evaluated on human lung carcinoma A549 cells and normal bronchial BEAS-2B cells. Designing the chemical structure of new antitumor agents the possible interactions with macromolecules such as DNA or proteins should be take into account. PCR gene tlr4 product served as DNA model, whereas lysozyme and phage-derived endolysin (both peptidoglycan degrading enzymes) were applied as protein/enzyme model. The interactions were analysed using PCR-HRM and circular dichroism, FT-IR, spectrophotometry, respectively. Additionally, the antimicrobial properties of the complexes at a non-cytotoxic concentration were analyzed against S. aureus, E. coli, P. aeruginosa and C. albicans strains. The results obtained in this study showed the selective cytotoxicity of metal complexes, mainly [Cu(1-allim)4 (NO3 )2 ] towards tumor cells. From all tested compounds, only [Co(iaa)2 (H2 O)2 ]. H2 O non-covalently interacts with DNA. Cu(II) and Co(II) complexes did not affect the secondary conformation of tested proteins but modified the hydrolytic activity of enzymes (lysozyme and endolysin). Moreover, only [Co(iaa)2 (H2 O)2 ]. H2 O exhibited the antifungal properties. In conclusion, Co(II) and Cu(II) metal complexes bearing two imidazole-4-acetate ligands seemed to be promising antitumor and antifungal agents for future drug design and application.- Published
- 2019
- Full Text
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30. Influence of PEGylation on Domain Dynamics of Phosphoglycerate Kinase: PEG Acts Like Entropic Spring for the Protein.
- Author
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Ciepluch K, Radulescu A, Hoffmann I, Raba A, Allgaier J, Richter D, and Biehl R
- Subjects
- Entropy, Enzyme Stability, Molecular Dynamics Simulation, Phosphoglycerate Kinase metabolism, Polyethylene Glycols metabolism, Protein Domains, Protein Structure, Secondary, Saccharomyces cerevisiae chemistry, Saccharomyces cerevisiae metabolism, Phosphoglycerate Kinase chemistry, Polyethylene Glycols chemistry, Saccharomyces cerevisiae enzymology
- Abstract
Protein-polymer conjugation is a widely used technique to develop protein therapeutics with improved pharmacokinetic properties as prolonged half-life, higher stability, water solubility, lower immunogenicity, and antigenicity. Combining biochemical methods, small angle scattering (SAXS/SANS), and neutron spin-echo spectroscopy, here we examine the impact of PEGylation (i.e., the covalent conjugation with poly(ethylene glycol) or PEG) on structure and internal domain dynamics of phosphoglycerate kinase (PGK) to elucidate the reason for reduced activity that is connected to PEGylation. PGK is a protein with a hinge motion between the two main domains that is directly related to function. We find that secondary structure and ligand access to the binding sites are not affected. The ligand induced cleft closing is unchanged. We observe an additional internal motion between covalent bonded PEG and the protein compatible with Brownian motion of PGK in a harmonic potential. Entropic interaction with the full PEG chain leads to a force constant of about 8 pN/nm independent of PEG chain length. This additional force preserves protein structure and has negligible effects on the functional domain dynamics of the protein. PEGylation seems to reduce activity just by acting as a local crowder for the ligands. The newly identified interaction mechanism might open possibilities to improve rational design of protein-polymer conjugates.
- Published
- 2018
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31. Dendrimers complexed with HIV-1 peptides interact with liposomes and lipid monolayers.
- Author
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Ionov M, Ciepluch K, Garaiova Z, Melikishvili S, Michlewska S, Balcerzak Ł, Glińska S, Miłowska K, Gomez-Ramirez R, de la Mata FJ, Shcharbin D, Waczulikova I, Bryszewska M, and Hianik T
- Subjects
- Dendrimers chemistry, Fluorescence Polarization, Humans, Hydrophobic and Hydrophilic Interactions, Lipid Bilayers chemistry, Liposomes, Membrane Fluidity, Membrane Lipids chemistry, Microscopy, Electron, Transmission, Peptide Fragments chemistry, Phospholipids chemistry, Phospholipids metabolism, Silanes chemistry, Dendrimers metabolism, HIV-1 chemistry, Lipid Bilayers metabolism, Membrane Lipids metabolism, Peptide Fragments metabolism, Silanes metabolism
- Abstract
Aims: We have investigated the effect of surface charge of model lipid membranes on their interactions with dendriplexes formed by HIV-derived peptides and 2 types of positively charged carbosilane dendrimers (CBD)., Methods: Interaction of dendriplexes with lipid membranes was measured by fluorescence anisotropy, dynamic light scattering and Langmuir-Blodgett techniques. The morphology of the complexes was examined by transmission electron microscopy., Results: All dendriplexes independent of the type of peptide interacted with model lipid membranes. Negatively charged vesicles composed of a mixture of DMPC/DPPG interacted more strongly, and it was accompanied by an increase in anisotropy of the fluorescent probe localized in polar domain of lipid bilayers. There was also an increase in surface pressure of the lipid monolayers. Mixing negatively charged liposomes with dendriplexes increased liposome size and made their surface charges more positive., Conclusions: HIV-peptide/dendrimer complexes interact with model lipid membranes depending on their surface charge. Carbosilane dendrimers can be useful as non-viral carriers for delivering HIV-peptides into cells., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
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32. Effect of viologen-phosphorus dendrimers on acetylcholinesterase and butyrylcholinesterase activities.
- Author
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Ciepluch K, Weber M, Katir N, Caminade AM, El Kadib A, Klajnert B, Majoral JP, and Bryszewska M
- Subjects
- Circular Dichroism, Dendrimers chemistry, Erythrocyte Membrane drug effects, Erythrocyte Membrane enzymology, Fluorescence, Humans, Phosphorus chemistry, Static Electricity, Viologens chemistry, Acetylcholinesterase metabolism, Butyrylcholinesterase metabolism, Dendrimers pharmacology, Phosphorus pharmacology, Viologens pharmacology
- Abstract
The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is the first step in checking whether new compounds can be considered as drugs for treating neurodegenerative diseases. The effect of viologen-phosphorus dendrimers on AChE and BChE activities was studied. The results show that the effects on the cholinesterase activities depend on dendrimer type and size. Viologen dendrimers can interact with the enzymes in two ways: they can bind either to a peripheral site of the enzyme or to amino acids located near the active site, inhibiting catalysis by both cholinesterases. All tested non-toxic viologen-phosphorus dendrimers inhibited the activities of both cholinesterases, showing their potential as new drugs for treating neurodegenerative diseases., (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Published
- 2013
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33. Complexation of HIV derived peptides with carbosilane dendrimers.
- Author
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Ionov M, Ciepluch K, Klajnert B, Glińska S, Gomez-Ramirez R, de la Mata FJ, Munoz-Fernandez MA, and Bryszewska M
- Subjects
- Amino Acid Sequence, Electrochemistry, Electrophoresis, Polyacrylamide Gel, Fluorescence Polarization, Indicators and Reagents, Microscopy, Electron, Transmission, Particle Size, Dendrimers chemistry, HIV-1 chemistry, Peptides chemistry, Silanes chemistry
- Abstract
Dendrimers have been proposed as new carriers for selected HIV-1 peptides. This paper reports on the complexation behaviour of the three HIV-derived-peptides: Gp160, NH-EIDNYTNTIYTLLEE-COOH; P24, NH-DTINEEAAEW-COOH and Nef, NHGMDDPEREVLEWRFDSRLAF-COOH with second generation cationic carbosilane dendrimers (CBD) branched with carbonsilicon bonds (CBD-CS) or oxygensilicon bonds (CBD-OS). Studies on the formation of complexes between HIV peptides and CBDs by fluorescence polarization, zeta-potential, electrophoresis and transmission electron microscopy have shown that both studied dendrimers form complexes with HIV peptides. At a molar ratio of (2.5-3):1 (dendrimer:peptide), the complexes formed were in the size range of 180-275 nm and with significant positive surface charge. The results suggest that interactions between dendrimers and HIV peptides have electrostatic nature due to the negative charge of peptides backbone and positive charge of dendrimer functional groups. Dendriplex stability depended on the type of studied dendrimers. Time of peptides release from the complexes ranged from 1 (CBD-OS) to ~36 (CBD-CS)h. Basing on the obtained results, we propose that the water-soluble cationic carbosilane dendrimers can be considered for delivery of HIV peptides to dendritic cells., (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Published
- 2013
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34. Modulation of biogenic amines content by poly(propylene imine) dendrimers in rats.
- Author
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Ciepluch K, Ziemba B, Janaszewska A, Appelhans D, Klajnert B, Bryszewska M, and Fogel WA
- Subjects
- Animals, Male, Organ Specificity, Rats, Rats, Wistar, Dendrimers pharmacology, Histamine metabolism, Polypropylenes pharmacology, Spermidine metabolism
- Abstract
Biogenic amines and polyamines participate in all vital organism functions, their levels being important function determinants. Studies were performed to check whether repeated administration of poly(propylene imine) (PPI) dendrimers, synthetic macromolecules with diaminobutane core, and peripheral primary amine groups, may influence the endogenous level of amines, as represented by the two of them: spermidine, a natural derivative of diaminobutane, and histamine. The experiment was carried out on Wistar rats. Fourth generation PPI dendrimer, as well as maltotriose-modified fourth generation PPI dendrimers with (a) cationic open sugar shell and (b) neutral dense sugar shell that possess a higher biocompatibility, was used. Applying the combination of column chromatography on Cellex P and spectrofluorimetric assays of o-phthaldialdehyde, the final amine condensation products were employed to analyze tissue spermidine and histamine outside the central nervous system. Furthermore, radioenzymatic assay was used to measure histamine levels in the brain. The obtained results indicate that in some tissues, the endogenous concentrations of histamine and spermidine may be affected by dendrimers depending on their dose and type of dendrimers.
- Published
- 2012
- Full Text
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35. Biological properties of new viologen-phosphorus dendrimers.
- Author
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Ciepluch K, Katir N, El Kadib A, Felczak A, Zawadzka K, Weber M, Klajnert B, Lisowska K, Caminade AM, Bousmina M, Bryszewska M, and Majoral JP
- Subjects
- Anti-Bacterial Agents adverse effects, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents pharmacology, Antifungal Agents adverse effects, Antifungal Agents chemistry, Antifungal Agents pharmacology, Dendrimers adverse effects, Dendrimers pharmacology, Erythrocytes drug effects, Humans, Microbial Sensitivity Tests, Molecular Structure, Dendrimers chemistry, Phosphorus chemistry, Viologens chemistry
- Abstract
Some biological properties of eight dendrimers incorporating both phosphorus linkages and viologen units within their cascade structure or at the periphery were investigated for the first time. In particular cytotoxicity, hemotoxicity, and antimicrobial and antifungal activity of these new macromolecules were examined. Even if for example all these species exhibited good antimicrobial properties, it was demonstrated that their behavior strongly depends on several parameters as their size and molecular weight, the number of viologen units and the nature of the terminal groups.
- Published
- 2012
- Full Text
- View/download PDF
36. In vivo toxicity of poly(propyleneimine) dendrimers.
- Author
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Ziemba B, Janaszewska A, Ciepluch K, Krotewicz M, Fogel WA, Appelhans D, Voit B, Bryszewska M, and Klajnert B
- Subjects
- Animals, Behavior, Animal drug effects, Body Weight drug effects, Drinking drug effects, Eating drug effects, Male, Materials Testing, Molecular Structure, Rats, Rats, Wistar, Dendrimers chemistry, Dendrimers toxicity, Polypropylenes chemistry, Polypropylenes toxicity
- Abstract
Dendrimers are highly branched macromolecules with the potential to be used for biomedical applications. Several dendrimers are toxic owing to their positively charged surfaces. However, this toxicity can be reduced by coating these peripheral cationic groups with carbohydrate residues. In this study, the toxicity of three types of 4th generation poly (propyleneimine) dendrimers were investigated in vivo; uncoated (PPI-g4) dendrimers, and dendrimers in which 25% or 100% of surface amino groups were coated with maltotriose (PPI-g4-25%m or PPI-g4-100%m), were administered to Wistar rats. Body weight, food and water consumption, and urine excretion were monitored daily. Blood was collected to investigate biochemical and hematological parameters, and the general condition and behavior of the animals were analyzed. Unmodified PPI dendrimers caused changes in the behavior of rats, a decrease in food and water consumption, and lower body weight gain. In the case of PPI-g4 and PPI-g4-25%m dendrimers, disturbances in urine and hematological and biochemical profiles returned to normal during the recovery period. PPI-g4-100%m was harmless to rats. The PPI dendrimers demonstrated dose- and sugar-modification-degree dependent toxicity. A higher dose of uncoated PPI dendrimers caused toxicity, but surface modification almost completely abolished this toxic effect., (Copyright © 2011 Wiley Periodicals, Inc.)
- Published
- 2011
- Full Text
- View/download PDF
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