Mariusz Kepczynski - Academia.edu (original) (raw)

Papers by Mariusz Kepczynski

ACS Omega, 2021

Nanoparticles made of amphiphilic block copolymers are commonly used in the preparation of nano-s... more Nanoparticles made of amphiphilic block copolymers are commonly used in the preparation of nano-sized drug delivery systems. Poly(styrene)−block−poly(acrylic acid) (PS−PAA) copolymers have been proposed for drug delivery purposes; however, the drug loading capacity and cytotoxicity of PS−PAA nanoparticles are still not fully recognized. Herein, we investigated the accumulation of a model hydrophobic drug, curcumin, and its spatial distribution inside the PS−PAA nanoparticles. Experimental methods and atomistic molecular dynamics simulations were used to understand the molecular structure of the PS core and how curcumin molecules interact and organize within the PS matrix. The hydrophobic core of the PS−PAA nanoparticles consists of adhering individually coiled polymeric chains and is compact enough to prevent postincorporation of curcumin. However, the drug has a good affinity for the PS matrix and can be efficiently enclosed in the PS−PAA nanoparticles at the formation stage. At low concentrations, curcumin is evenly distributed in the PS core, while its aggregates were observed above ca. 2 wt %. The nanoparticles were found to have relatively low cytotoxicity to human skin fibroblasts, and the presence of curcumin further increased their biocompatibility. Our work provides a detailed description of the interactions between a hydrophobic drug and PS−PAA nanoparticles and information on the biocompatibility of these anionic nanostructures which may be relevant to the development of amphiphilic copolymer-based drug delivery systems.

Australian Endodontic Journal, 2021

The aim was to assess the impact of irrigation protocols ended with ethanol or chlorhexidine on A... more The aim was to assess the impact of irrigation protocols ended with ethanol or chlorhexidine on AH Plus penetration into dentinal tubules. 45 root canals were prepared to ISO 40/04, divided into three groups and irrigated with three protocols: Group 1 (control): 5.25% NaOCl; Group 2: 40% CA (citric acid), 5.25% NaOCl, 40% CA, water, ethanol; Group 3: 40% CA, 5.25% NaOCl, 40% CA, water, 2% chlorhexidine. Canals were filled using vertical condensation technique with gutta-percha and fluorescein-stained AH Plus sealer. After 72 h, 1 mm thick cross-sections were cut at 2, 5, 8 mm from the apex. Confocal laser microscope was used to measure the sealer penetration into dentinal tubules. Mean depth of sealer penetration (in micrometres) was 107, 131, 170 (Group 1); 146, 233, 317 (Group 2); 185, 301, 542 (Group 3); in apical, middle and coronal parts, respectively. Irrigation protocol ended with chlorhexidine resulted in the deeper sealer penetration compared with alcohol.

Chemistry and Physics of Lipids, 2019

The Journal of Physical Chemistry B, 2018

The journal of physical chemistry. B, Jan 19, 2017

Interaction of polycations with lipid membranes is a very important issue in many biological and ... more Interaction of polycations with lipid membranes is a very important issue in many biological and medical applications such as gene delivery or antibacterial usage. In this work, we address the influence of hydrophobic substitution of strong polycations containing quaternary ammonium groups on the polymer-zwitterionic membrane interactions. In particular, we focus on the polymer tendency to adsorb on or/and incorporate into the membrane. We used complementary experimental and computational methods to enhance our understanding of the mechanism of the polycation-membrane interactions. Polycation adsorption on liposomes was assessed using dynamic light scattering (DLS) and zeta potential measurements. The ability of the polymers to form hydrophilic pores in the membrane was evaluated using a calcein-release method. The polymer-membrane interaction at the molecular scale was explored by performing atomistic molecular dynamics (MD) simulations. Our results show that the length of the alky...

Colloids and surfaces. B, Biointerfaces, Jan 19, 2017

Polymer vesicles formed by a pair of oppositely charged diblock copolyelectrolytes (PICsomes) are... more Polymer vesicles formed by a pair of oppositely charged diblock copolyelectrolytes (PICsomes) are considered as a good alternative to polymersomes formed by amphiphilic copolymers. Here, we report on inherent stability and in vitro biocompatibility of PICsomes prepared from a pair of oppositely charged zwitterionic-ionic copolymers, in which the ionic block is a strong polyelectrolyte. Our results demonstrated that the PICsomes are highly stable over a wide range of pH and temperatures. Direct microscopic observations revealed that the PICsomes retain their morphology in the presence of human serum. In vitro studies using human skin fibroblasts (HSFs) showed that the polymer vesicles are not cytotoxic and do not affect cell proliferation and adhesion. A model hydrophilic dye was effectively incorporated into the PICsomes by simple mixing. Using confocal microscopy observations, we demonstrated that the dye-loaded PICsomes are efficiently internalized by the cells and are located pre...

Molecular pharmaceutics, Jan 3, 2017

Itraconazole (ITZ) is an antifungal agent used clinically to treat mycotic infections. However, i... more Itraconazole (ITZ) is an antifungal agent used clinically to treat mycotic infections. However, its therapeutic effects are limited by low solubility in aqueous media. Liposome-based delivery systems (LDS) have been proposed as a delivery mechanism for ITZ to alleviate this problem. Furthermore, PEGylation, the inclusion in the formulation of a protective "stealth sheath" of poly(ethylene glycol) around carrier particles, is widely used to increase circulation time in the bloodstream and hence efficacy. Together, these themes highlight the importance of mechanistic and structural understanding of ITZ incorporation into liposomes both with and without PEGylation because it can provide a potential foundation for the rational design of LDS-based systems for delivery of ITZ, using alternate protective polymers or formulations. Here we have combined atomistic simulations, cryo-TEM, Langmuir film balance, and fluorescence quenching experiments to explore how ITZ interacts with b...

Colloids and Surfaces B: Biointerfaces, 2017

Biocompatible and fluorescent superparamagnetic iron oxide nanoparticles with superior magnetic p... more Biocompatible and fluorescent superparamagnetic iron oxide nanoparticles with superior magnetic properties coated with charged polysaccharide derivatives

Journal of Materials Chemistry B, 2015

Novel biocompatible polymersomes with semipermeable ionic membranes were used as promising delive... more Novel biocompatible polymersomes with semipermeable ionic membranes were used as promising delivery systems.

Mikrochimica acta, 2015

Fluorescence and surface-enhanced Raman scattering (SERS) spectroscopy were employed to investiga... more Fluorescence and surface-enhanced Raman scattering (SERS) spectroscopy were employed to investigate the cellular uptake of rhodamine 6G (R6G) alone and of R6G loaded with gold nanoparticles (AuNPs) by endothelial cells. R6G plays the role of a Raman reporter in SERS but also displays strong fluorescence. The presence of bare R6G molecules and R6G-AuNPs in the cytoplasm of the cells is detected via the 2D fluorescence of the dye after a 0.5 h of the incubation with R6G and R6G-AuNPs, and then the concentration of the dye increases within 4 h of exposure. The examination of the cellular uptake of the R6G and R6G-AuNPs species at different temperatures suggests that the internalization of the R6G-AuNPs into endothelial cells occurs mainly via endocytosis. 3D fluorescence imaging of R6G inside cells reveals inhomogeneous distribution of the dye in the cytoplasm. The SERS signal of the Raman reporter inside the cell disappears after 2 h of incubation with R6G-AuNPs and then amino acid re...

Pure and Applied Chemistry, 2001

Novel polymeric photosensitizers for singlet oxygen production in water are described. The polyme... more Novel polymeric photosensitizers for singlet oxygen production in water are described. The polymers contain rose bengal (4,5,6,7-tetrachloro-2',4',5',7'tetraiodo-fluorescein) chromophores covalently attached to the polymer chain. The quantum yields of singlet oxygen formation and photooxidation of phenol in water have been determined. The methods of separation of photosensitizer from the reactants after completion of reaction have been established.

Colloids and surfaces. B, Biointerfaces, 2014

Liposomes are used for in vitro or in vivo vectorization of drugs, proteins, or nucleic acids. Ho... more Liposomes are used for in vitro or in vivo vectorization of drugs, proteins, or nucleic acids. However, the main problem with the application of liposomes for this purpose is their low stability in contact with blood serum. In this article, interactions between the whole serum and anionic liposomes, both bare and covered with strong polycations, were studied. The polycations of different chemical structures were prepared by the modification of poly(allylamine hydrochloride) (PAH). Dynamic light scattering (DLS), zeta potential and transmission cryo-electron microscopy (cryo-TEM) measurements showed that the adsorption of the polycations on the anionic liposomes induced a reversible aggregation of vesicles. The stable isolated polyelectrolyte-covered vesicles were obtained after the addition of sufficient amounts of the polycations. The effect of full serum on the morphology and stability of the polycation-coated liposomes was studied using cryo-TEM and a fluorescence method. The cry...

Toxicon, 2001

A novel and promising method of microcystin-LR (mcyst-LR) degradation is reported. The decomposit... more A novel and promising method of microcystin-LR (mcyst-LR) degradation is reported. The decomposition of this cyanobacterial toxin using Fenton reagent has been observed with very low initial concentrations of H2O2 and Fe2+ (Fe3+) in the reaction mixture. Mcyst-LR was isolated from a laboratory culture of Microcystis aeruginosa PCC 7813. The initial concentration of the toxin used exceeded by several orders of magnitude those occurring naturally in lakes and drinking water. Even so, the decomposition of the toxin was complete after 30 min.

Theriogenology, 2011

The principal objective of this study was to develop a novel method based on confocal microscopy ... more The principal objective of this study was to develop a novel method based on confocal microscopy and a solvatochromic fluorescent dye, Nile red (NR) to quantify the main types of lipids in a single mammalian oocyte and embryo. We hypothesize that NR staining followed by the decomposition of NR-spectra identifies and quantifies the triglycerides, phospholipids, and cholesterol in a single oocyte and embryo. We analyzed the lipid droplets in porcine oocytes and pre-implantation embryos up to the hatched blastocyst stage developed in vivo and in cultured blastocysts. The emission spectrum of NR-stained mixture of different lipid types is a convolution of several component spectra. The principal component analysis (PCA) and a multivariate curve resolution-alternating least squares method (MCR-ALS) allowed to decompose the emission spectrum and quantify the relative amount of each lipid type present in mixture. We reported here that the level of the triglycerides, phospholipids and cholesterol in lipid droplets significantly decreases by 17.7%, 26.4% and 23.9%, respectively, from immature to mature porcine oocytes. The content of triglycerides and phospholipids remains unchanged in droplets of embryos from the zygote up to the morula stage. Then the triglyceride level decreases in the blastocyst by 15.1% and in the hatched blastocyst by 37.3%, whereas the amount of phospholipids decreases by 10.5% and 12.5% at the blastocyst and hatched blastocyst stages, respectively. In contrast, the content of cholesterol in droplets does not change during embryo cleavage. The lipid droplets in the blastocyst produced in vivo contain lower amounts of triglycerides (by 26.1%), phospholipids (by 14.2%) and cholesterol (by 34.8%) than those in the blastocyst cultured in NCSU-23 medium. In conclusion, our new technique is suitable to quantify the content of triglycerides, phospholipids and cholesterol in individual mammalian oocytes and embryos. Our findings indicate an important role for lipids during porcine oocyte maturation and early embryonic development, and suggest an altered lipid metabolism in cultured embryos.

The Journal of Physical Chemistry C, 2014

ABSTRACT A new type of hybrid photosensitizer (Po–C30B) was obtained by efficient adsorption of a... more ABSTRACT A new type of hybrid photosensitizer (Po–C30B) was obtained by efficient adsorption of a 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (Po) by Cloisite 30B (C30B)—a monotallow bis(hydroxyethyl)ammonium-modified montmorillonite clay—from acidic solution in methanol. Structural and spectroscopic properties of Po-nanoclay photosensitizer were determined using X-ray diffraction, laser scanning fluorescence confocal microscopy, and electronic absorption/emission spectroscopies. Po is present not only at the surface of the nanoclay but also in the interior of the Po-C30B hybrid material. The obtained material was found to be an efficient photosensitizer for the oxidation of phenol in aqueous solution under irradiation with the visible light (λ > 470 nm). The mechanism and the quantum yield of that process were shown to be strongly pH-dependent. They were controlled by the acid–base equilibria of porphyrin associated with imine N-protonation as well as by the ionization of the phenol molecule. The quantitative information regarding these dependencies was obtained. The values of K3 and K4 acid–base equilibrium constants were determined (pK3 = 5.88 and pK4 = 2.46) from the absorption spectra recorded during acid–base titration and using an evolutionary factor analysis with the mathematical model including dicationic (H2Po2+), monocationic (HPo+), and neutral (Po) porphyrin forms. They were used to evaluate the importance of these forms in singlet oxygen generation by Po–C30B under defined pH conditions. Moreover, the hybrid photosensitizer can be used repeatedly, which makes it possible to use it in industrial applications.

The Journal of Physical Chemistry B, 2014

Poly(ethylene glycol) (PEG) is a polymer commonly used for functionalization of drug molecules to... more Poly(ethylene glycol) (PEG) is a polymer commonly used for functionalization of drug molecules to increase their bloodstream lifetime, hence efficacy. However, the interactions between the PEGylated drugs and biomembranes are not clearly understood. In this study, we employed atomic-scale molecular dynamics (MD) simulations to consider the behavior of two drug molecules functionalized with PEG (tetraphenylporphyrin used in cancer phototherapy and biochanin A belonging to the isoflavone family) in the presence of a lipid bilayer. The commonly held view is that functionalization of a drug molecule with a polymer acts as an entropic barrier, inhibiting the penetration of the drug molecule through a cell membrane. Our results indicate that in the bloodstream there is an additional source of electrostatic repulsive interactions between the PEGylated drugs and the lipid bilayer. Both the PEG chain and lipids can bind Na(+) ions, thus effectively becoming positively charged molecules. This leads to an extra repulsive effect resulting from the presence of salt in the bloodstream. Thus, our study sheds further light on the role of PEG in drug delivery.