Karolina H. Markiewicz

Nanoparticles as drug delivery systems

Controlled drug delivery systems (DDS) have several advantages compared to the traditional forms of drugs. A drug is transported to the place of action, hence, its influence on vital tissues and undesirable side effects can be minimized. Accumulation of therapeutic compounds in the target site increases and, consequently, the required doses of drugs are lower. This modern form of therapy is especially important when there is a discrepancy between the dose or the concentration of a drug and its therapeutic results or toxic effects. Cell-specific targeting can be accomplished by attaching drugs to specially designed carriers. Various nanostructures, including liposomes, polymers, dendrimers, silicon or carbon materials, and magnetic nanoparticles, have been tested as carriers in drug delivery systems. In this review, the aforementioned nanocarriers and their connections with drugs are analyzed. Special attention is paid to the functionalization of magnetic nanoparticles as carriers in DDS. Then, the advantages and disadvantages of using magnetic nanoparticles as DDS are discussed.

Magnetic nanoparticles as new diagnostic tools in medicine

Magnetic iron oxide nanoparticles have raised much interest during the recent years due to their novel properties (superparamagnetism, high saturation field, blocking temperature, etc.) and potential applications in organic synthesis, biotechnology and finally in medicine. The medicinal applications include: controlled drug delivery systems (DDS), magnetic resonance imaging (MRI), magnetic fluid hyperthermia (MFH), macromolecules and pathogens separation, cancer therapy and so on. In this paper we would like to present the newest literature reports concerning usage of MNPs in medicinal diagnostics such as: - magnetic separations of DNA (immobilization, isolation, diagnosis of genetic disorders and detection of exogenous substances in the organisms) - magnetic immobilization of proteins (applications in biotechnology, medicine, and catalysis) - magnetic separations of pathogens (i.e. isolation of bacteria, detection of various pathogens) - magnetic resonance imaging (imaging contrast agents, lymphangiography).

Growth arrest and rapid capture of select pathogens following magnetic nanoparticle treatment.

Thorough understanding of magnetic nanoparticle (MNP) properties is essential for developing new theranostics. In this study, we provide evidence that non-modified magnetic iron oxide nanoparticles and their functionalized derivatives may be used to restrict growth and capture different pathogens. Coprecipitation of Fe(2+) and Fe(3+) ions in an alkaline solution was used to synthesize MNPs that subsequently were functionalized by gold and aminosilane coating. Transmission electron microscopy (TEM), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR) were used to assess their physicochemical properties. A significant decrease of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans outgrown from medium after addition of MNPs or their derivatives was observed during 24h culture. Measurement of optical density revealed that using MNPs, these pathogens can be quickly captured and removed (with efficiency reaching almost 100%) from purposely infected saline buffer and body fluids such as human blood plasma, serum, abdominal fluids and cerebrospinal fluids. These effects depend on nanoparticle concentration, surface chemistry, the type of pathogen, as well as the surrounding environment.

Aggregation of gluten proteins in model dough after fibre polysaccharide addition

FT-Raman spectroscopy, thermogravimetry and differential scanning calorimetry were used to study changes in structure of gluten proteins and their thermal properties influenced by four dietary fibre polysaccharides (microcrystalline cellulose, inulin, apple pectin and citrus pectin) during development of a model dough. The flour reconstituted from wheat starch and wheat gluten was mixed with the polysaccharides in five concentrations: 3%, 6%, 9%, 12% and 18%. The obtained results showed that all polysaccharides induced similar changes in secondary structure of gluten proteins concerning formation of aggregates (1604cm-1), H-bonded parallel- and antiparallel-β-sheets (1690cm-1) and H-bonded β-turns (1664cm-1). These changes concerned mainly glutenins since β-structures are characteristic for them. The observed structural changes confirmed hypothesis about partial dehydration of gluten network after polysaccharides addition. The gluten aggregation and dehydration processes were also reflected in the DSC results, while the TGA ones showed that gluten network remained thermally stable after polysaccharides addition.

Core–shell magnetic nanoparticles display synergistic antibacterial effects against Pseudomonas aeruginosa and Staphylococcus aureus when combined with cathelicidin LL-37 or selected ceragenins

Core–shell magnetic nanoparticles (MNPs) are promising candidates in the development of new treatment methods against infections, including those caused by antibiotic-resistant pathogens. In this study, the bactericidal activity of human antibacterial peptide cathelicidin LL-37, synthetic ceragenins CSA-13 and CSA-131, and classical antibiotics vancomycin and colistin, against methicillin-resistant Staphylococcus aureus Xen 30 and Pseudomonas aeruginosa Xen 5, was assessed alone and in combination with core–shell MNPs. Fractional inhibitory concentration index and fractional bactericidal concentration index were determined by microdilution methods. The potential of combined therapy using nanomaterials and selected antibiotics was confirmed using chemiluminescence measurements. Additionally, the ability of tested agents to prevent bacterial biofilm formation was evaluated using crystal violet staining. In most conditions, synergistic or additive effects were observed when combinations of core–shell MNPs with ceragenins or classical antibiotics were used. Our study revealed that a mixture of membrane-active agents such as LL-37 peptide or ceragenin CSA-13 with MNPs potentialized their antibacterial properties and might be considered as a method of delaying and overcoming bacterial drug resistance.

Advantages of poly(vinyl phosphonic acid)-based double hydrophilic block copolymers for the stabilization of iron oxide nanoparticles

Poly(ethylene glycol)–poly(vinylphosphonic acid) block copolymers (PEG-b-PVPA) of low average molar mass were synthesized by RAFT/MADIX polymerization. Their intrinsic properties (i.e. anionic-neutral character which brings both ability to strongly interact with cations and steric stabilization) allow the one-step in situ synthesis of water-dispersible iron oxide nanoparticles with controlled size and high colloidal stability. The effect of structural properties of the polymer (chain length of PEG and PVPA blocks) on the formation and/or stabilization of nanoparticles has been evaluated. Additionally, PVPA and PAA block complexing abilities were compared and the advantage of phosphonic acid groups over carboxylic acid groups was proven. Hemocompatibility tests carried out with the DHBCs alone and DHBC/iron oxide hybrid nanoparticles revealed that the hemolysis rates observed with phosphonated copolymers were much lower than for their carboxylated analogs.

New acetylacetone-polymer modified nanoparticles as magnetically separable complexing agents

In this paper, we present two methods of synthesis of new bifunctional polymeric nanohybrids and their full characterization. These nanohybrids consist of a magnetic nanoparticle core and polymeric shell which possess the ability to complex metal ions and organic compounds. Synthesized materials exhibit superparamagnetic properties and can thus be easily separated from complex mixtures by using an external magnetic field (facile separation, purification and recyclability). Herein, the syntheses of three bifunctional monomers are presented. Each of them was used to prepare the homopolymeric shell and two types of copolymeric shells (using styrene as a comonomer) around the magnetite nanoparticles. A surface initiated RAFT/MADIX polymerization technique was employed to prepare polymeric shells. Afterwards, post-modification of azide functionalized polymeric shells using the Huisgen “click” reaction was performed. Finally, twelve types of nanohybrids were prepared and their physicochemical properties were investigated. Additionally, the ability of nanohybrids to complex lanthanides and spectroscopic properties of obtained materials were studied.

Magnetic nanoparticles with chelating shells prepared by RAFT/MADIX polymerization

In this study, the preparation of multifunctional materials based on magnetic nanoparticles (MNP) and original thiosemicarbazide derivatives is presented. The synthesized nanohybrids consist of an iron oxide core and a polymeric shell, which possesses the ability to complex metal ions. They exhibit superparamagnetic properties and can thus be easily separated from complex mixtures using an external magnetic field (facile separation, purification, and recyclability). Synthesized carbamohydrazonothioate derivatives were polymerized on dithiocarbonate-coated MNPs using the RAFT/MADIX (reversible addition–fragmentation transfer/macromolecular design by interchange of xanthates) method. Three types of nanohybrids were obtained and their physicochemical properties were investigated. The ability of nanohybrids to complex palladium(II) ions and the spectroscopic properties of the obtained materials were studied. In addition, the hemolytic activity tests of polymer-coated particles were performed in order to confirm their potential in biomedical applications.

Ring-opening reactions of epoxidized SWCNT with nucleophilic agents: a convenient way for sidewall functionalization

The rational chemical modification of carbon nanotubes (CNT) is crucial for their successful application in various areas of science and industry. In our approach, Birch reduction of single-walled carbon nanotubes (SWCNT) was followed by epoxidation with dimethyldioxirane (DMDO). Next, ring-opening reactions with thiosemicarbazide, p-phenylenediamine, aminosilica-coated magnetic nanoparticles, propargyl alcohol, 6-bromohexanoic acid, and ethyl potassium dithiocarbonate were performed, which resulted in a wide variety of functional groups being covalently anchored to the sidewalls of the nanotubes. Raman spectroscopy, Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible-near infrared spectroscopy (UV-Vis-NIR), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), and transmission electron microscopy (TEM) were employed to confirm modifications and study the chemical composition of the obtained structures.

Carbamohydrazonothioate derivative—experimental and theoretical explorations of the crystal and molecular structure

AbstractThe structural studies of carbamohydrazonothioate derivative and its hydrochloride solvate are the aim of hereunder presented research. The combination of the crystallographic technics and the Hirshfeld surface analysis allows to describe the net of the hydrogen bonds as well as other non-covalent interactions within the crystal structures. The crystal structures of 4-ethenylbenzyl N′-[(E)-phenylmethylidene] carbamohydrazonothioate (CHT) and CHT hydrochloride solvate are built of bent and linear conformers of the carbamohydrazonothioate derivative, respectively. The theoretical calculations indicate that the alteration of the conformation is possible. While the geometry of the bent conformers allows the crystal structure to propagate, the linear conformation does not encourage formation of the intermolecular interactions between CHT molecules. Therefore, in the latter case, the chloride ions and methanol play the role of the molecular glue. In both crystal structures, the dominant is H···H interaction; thus, the dispersion energy is an important factor in intermolecular interactions. The theoretical calculations for single molecules and dimers of CHT show the negligible influence of the crystal packing on molecular conformation and dimer formation, when the dispersion energy correction is applied.