Liposomes are one of the most important drug delivery vectors, nowadays used in clinics. In general, polyethylene glycol (PEG) is used to ensure the stealth properties of the liposomes. Here, we have employed hydrophilic, biocompatible and highly non-fouling N-(2-hydroxypropyl) methacrylamide (HPMA)-based copolymers containing hydrophobic cholesterol anchors for the surface modification of liposomes, which were prepared by the method of lipid film hydration and extrusion through 100 nm polycarbonate filters. Efficient surface modification of liposomes was confirmed by transmission electron microscopy, atomic force microscopy, and gradient ultracentrifugation. The ability of long-term circulation in the vascular bed was demonstrated in rabbits after i.v. application of fluorescently labelled liposomes. Compared to PEGylated liposomes, HPMA-based copolymer-modified liposomes did not induce specific antibody formation and did not activate murine and human complement. Compared with PEGylated liposomes, HPMA-based copolymer-modified liposomes showed a better long-circulating effect after repeated administration. HPMA-based copolymer-modified liposomes thus represent suitable new candidates for a generation of safer and improved liposomal drug delivery platforms.
- MeSH
- Acrylamides chemistry MeSH
- Complement Activation drug effects MeSH
- Cholesterol chemistry blood MeSH
- Hydrophobic and Hydrophilic Interactions * MeSH
- Rabbits MeSH
- Drug Delivery Systems MeSH
- Humans MeSH
- Liposomes * MeSH
- Mice MeSH
- Polyethylene Glycols * chemistry MeSH
- Polymers chemistry MeSH
- Surface Properties * MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Humans MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Protein-repulsive surfaces modified with ligands for cell adhesion receptors have been widely developed for controlling the cell adhesion and growth in tissue engineering. However, the question of matrix production and deposition by cells on these surfaces has rarely been addressed. In this study, protein-repulsive polydopamine-poly(ethylene oxide) (PDA-PEO) surfaces were functionalized with an RGD-containing peptide (RGD), with a collagen-derived peptide binding fibronectin (Col), or by a combination of these peptides (RGD + Col, ratio 1:1) in concentrations of 90 fmol/cm(2) and 700 fmol/cm(2) for each peptide type. When seeded with vascular endothelial CPAE cells, the PDA-PEO surfaces proved to be completely non-adhesive for cells. On surfaces with lower peptide concentrations and from days 1 to 3 after seeding, cell adhesion and growth was restored practically only on the RGD-modified surface. However, from days 3 to 7, cell adhesion and growth was improved on surfaces modified with Col and with RGD + Col. At higher peptide concentrations, the cell adhesion and growth was markedly improved on all peptide-modified surfaces in both culture intervals. However, the collagen-derived peptide did not increase the expression of fibronectin in the cells. The deposition of fibronectin on the material surface was generally very low and similar on all peptide-modified surfaces. Nevertheless, the RGD + Col surfaces exhibited the highest cell adhesion stability under a dynamic load, which correlated with the highest expression of talin and vinculin in the cells on these surfaces. A combination of RGD + Col therefore seems to be the most promising for surface modification of biomaterials, e.g. vascular prostheses.
- MeSH
- Adsorption MeSH
- Biomimetics * MeSH
- Cell Adhesion * MeSH
- Gene Expression MeSH
- Fibronectins chemistry genetics MeSH
- Indoles chemistry MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Molecular Sequence Data MeSH
- Oligopeptides chemistry MeSH
- Polyethylene Glycols chemistry MeSH
- Polymers chemistry MeSH
- Surface Properties MeSH
- Amino Acid Sequence MeSH
- Talin genetics MeSH
- Vinculin genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Carbon quantum dots (CQDs) have great potential to be utilized as an optical sensing probe due to its unique photoluminescence and less toxic properties. This work reports a simple and novel synthesis method of carbon dots via direct acid hydrolysis in presence of polyethylene glycol (PEG), polyvinylpyrrolidone (PVP) and bovine serum albumin protein (BSA). In this study, fluorescent CQDs were synthesized by using citric acid and ascorbic acid as the source of carbon precursors, which was covered with polyethylene glycol (PEG), polyvinylpyrrolidone (PVP) and with bovine serum albumin (BSA), by microwave irradiation. Furthermore, the synthesis parameters as power, reaction time and temperature were studied and quality of prepared CQDs were investigated by spectral methods. Short reaction time (20 min) and temperature from 120 ºC to 140 ºC under microwave irradiation are sufficient to prepare luminescence carbon quantum dots. Absorption spectra and photoluminescence spectra were measured to characterize prepared dots in water solution. The photoluminescence spectra of CQDs doped with different protection compound show the different luminescent and excitation wavelengths starting from 330 nm to 430 nm. Importantly, these CQDs are demonstrated to be excellent bioimaging agents and fluorescent ink due to their stable emission, well dispersibility, low toxicity, long emission life time, and good compatibility with different macromolecules.
- MeSH
- Fluorescence MeSH
- Quantum Dots * MeSH
- Ascorbic Acid MeSH
- Citric Acid MeSH
- Microwaves MeSH
- Polyethylene Glycols MeSH
- Povidone MeSH
- Surface Properties * MeSH
- Serum Albumin, Bovine MeSH
- Spectrophotometry statistics & numerical data MeSH
- Chemistry Techniques, Synthetic MeSH
- Temperature MeSH
- Carbon * MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
Introduction.Staphylococcus aureus (SA) and Staphylococcus epidermidis (SE) are the most common pathogens from the genus Staphylococcus causing biofilm-associated infections. Generally, biofilm-associated infections represent a clinical challenge. Bacteria in biofilms are difficult to eradicate due to their resistance and serve as a reservoir for recurring persistent infections.Gap Statement. A variety of protocols for in vitro drug activity testing against staphylococcal biofilms have been introduced. However, there are often fundamental differences. All these differences in methodical approaches can then be reflected in the form of discrepancies between results.Aim. In this study, we aimed to develop optimal conditions for staphylococcal biofilm formation on pegs. The impact of peg surface modification was also studied.Methodology. The impact of tryptic soy broth alone or supplemented with foetal bovine serum (FBS) or human plasma (HP), together with the impact of the inoculum density of bacterial suspensions and the shaking versus the static mode of cultivation, on total biofilm biomass production in SA and SE reference strains was studied. The surface of pegs was modified with FBS, HP, or poly-l-lysine (PLL). The impact on total biofilm biomass was evaluated using the crystal violet staining method and statistical data analysis.Results. Tryptic soy broth supplemented with HP together with the shaking mode led to crucial potentiation of biofilm formation on pegs in SA strains. The SE strain did not produce biofilm biomass under the same conditions on pegs. Preconditioning of peg surfaces with FBS and HP led to a statistically significant increase in biofilm biomass formation in the SE strain.Conclusion. Optimal cultivation conditions for robust staphylococcal biofilm formation in vitro might differ among different bacterial strains and methodical approaches. The shaking mode and supplementation of cultivation medium with HP was beneficial for biofilm formation on pegs for SA (ATCC 29213) and methicillin-resistant SA (ATCC 43300). Peg conditioning with HP and PLL had no impact on biofilm formation in either of these strains. Peg coating with FBS showed an adverse effect on the biofilm formation of these strains. By contrast, there was a statistically significant increase in biofilm biomass production on pegs coated with FBS and HP for SE (ATCC 35983).
- MeSH
- Bacteriological Techniques instrumentation methods MeSH
- Biofilms classification drug effects growth & development MeSH
- Biomass MeSH
- Species Specificity MeSH
- Culture Media chemistry pharmacology MeSH
- Humans MeSH
- Extracellular Polymeric Substance Matrix classification drug effects MeSH
- Staphylococcus classification drug effects physiology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Magnetite (Fe3O4) nanoparticles with uniform sizes of 10, 20, and 31 nm were prepared by thermal decomposition of Fe(III) oleate or mandelate in a high-boiling point solvent (>320 °C). To render the particles with hydrophilic and antifouling properties, their surface was coated with a PEG-containing bisphosphonate anchoring group. The PEGylated particles were characterized by a range of physicochemical methods, including dynamic light scattering, transmission electron microscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy, and magnetization measurements. As the particle size increased from 10 to 31 nm, the amount of PEG coating decreased from 28.5 to 9 wt.%. The PEG formed a dense brush-like shell on the particle surface, which prevented particles from aggregating in water and PBS (pH 7.4) and maximized the circulation time in vivo. Magnetic resonance relaxometry confirmed that the PEG-modified Fe3O4 nanoparticles had high relaxivity, which increased with increasing particle size. In the in vivo experiments in a mouse model, the particles provided visible contrast enhancement in the magnetic resonance images. Almost 70% of administrated 20-nm magnetic nanoparticles still circulated in the blood stream after four hours; however, their retention in the tumor was rather low, which was likely due to the antifouling properties of PEG.
- MeSH
- Diphosphonates chemistry MeSH
- Magnetic Resonance Imaging MeSH
- Magnetite Nanoparticles chemistry ultrastructure MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Polyethylene Glycols chemistry MeSH
- Tissue Distribution MeSH
- Microscopy, Electron, Transmission MeSH
- Particle Size MeSH
- Ferric Compounds MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
We report novel pH-reversibly surface-shielded polyplexes with enhanced gene transfer activity upon systemic administration. A four-arm-structured sequence-defined cationic oligomer KK[HK[(H-Sph-K)3HC]2]2 was designed and synthesized on solid-phase, containing additional lysine residues not only for improved pDNA polyplex stability, but also providing attachment points for subsequent polyplex functionalization with amine-reactive shielding polymers. Herein, the surface of polyplexes was shielded with hydrophilic polymers, monovalent PEG or monovalent and multivalent pHPMA, optionally attached to the polyplex via the acid-labile linker AzMMMan. Overall, surface modification with PEG or pHPMA resulted in a decrease in the zeta potential of polyplexes, consistent with the degree of surface shielding. At pH 6.0, only polyplexes modified via the acid-labile linkage showed an increase in zeta potential, consistent with a "deshielding" in acidic environment, expected as beneficial for endosomal escape. Shielding was more efficient for multivalent pHPMA (20kDa, 30kDa) as compared to monovalent pHPMA (10kDa, 20kDa, 30kDa) or PEG (5kDa). In vitro transfection studies revealed higher gene expression by the polyplexes with the acid-labile shield as compared to their irreversibly shielded counterparts. Intravenous administration of AzMMMan-pHPMA modified polyplexes in an in vivo tumor mouse model mediated enhanced gene expression in the subcutaneous tumor and reduced undesirable expression in the liver.
The use of PBS, 10% FBS or 10% CS as media for SI-ATRP is reported. Controlled/living SI-ATRP of MeOEGMA in PBS is achieved leading to better control than in water. The livingness is confirmed by chain extension with MeOEGMA or carboxybetaine acrylamide. This technique is successfully adopted for the polymerization of MeOEGMA in 10% FBS or CS as models for complex biological media with reasonable control of the brush growth. All prepared brushes show excellent antifouling properties.
- MeSH
- Adsorption MeSH
- Acrylamides chemistry MeSH
- Biocompatible Materials chemical synthesis MeSH
- Blood Proteins chemistry MeSH
- Methacrylates chemistry MeSH
- Polyethylene Glycols chemistry MeSH
- Polymerization MeSH
- Buffers MeSH
- Serum MeSH
- Cattle MeSH
- Spectroscopy, Fourier Transform Infrared MeSH
- Materials Testing MeSH
- Water MeSH
- Gold chemistry MeSH
- Animals MeSH
- Check Tag
- Cattle MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The attractiveness of synthetic polymers for cell colonization can be affected by physical, chemical, and biological modification of the polymer surface. In this study, low-density polyethylene (LDPE) was treated by an Ar(+) plasma discharge and then grafted with biologically active substances, namely, glycine (Gly), polyethylene glycol (PEG), bovine serum albumin (BSA), colloidal carbon particles (C), or BSA+C. All modifications increased the oxygen content, the wettability, and the surface free energy of the materials compared to the pristine LDPE, but these changes were most pronounced in LDPE with Gly or PEG, where all the three values were higher than in the only plasma-treated samples. When seeded with vascular smooth muscle cells (VSMCs), the Gly- or PEG-grafted samples increased mainly the spreading and concentration of focal adhesion proteins talin and vinculin in these cells. LDPE grafted with BSA or BSA+C showed a similar oxygen content and similar wettability, as the samples only treated with plasma, but the nano- and submicron-scale irregularities on their surface were more pronounced and of a different shape. These samples promoted predominantly the growth, the formation of a confluent layer, and phenotypic maturation of VSMC, demonstrated by higher concentrations of contractile proteins alpha-actin and SM1 and SM2 myosins. Thus, the behavior of VSMC on LDPE can be regulated by the type of bioactive substances that are grafted.
- MeSH
- Aorta cytology drug effects MeSH
- Biocompatible Materials chemistry pharmacology MeSH
- Cell Adhesion drug effects MeSH
- Glycine chemistry pharmacology MeSH
- Rats MeSH
- Cells, Cultured MeSH
- Myocytes, Smooth Muscle cytology drug effects MeSH
- Polyethylene chemistry pharmacology MeSH
- Polyethylene Glycols chemistry pharmacology MeSH
- Surface Properties MeSH
- Cell Proliferation drug effects MeSH
- Serum Albumin, Bovine chemistry pharmacology MeSH
- Muscle, Smooth, Vascular cytology drug effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
In this work, a unique high-performance liquid chromatographic method was developed and applied for monitoring the synthesis of polyethyleneglycol surface modified poly(amidoamine) cystamine core dendrimers (PEG-PAMAMs) and PEG-PAMAM-alkynes with a single alkyne moiety attached to the core of a dendron through a unique sulfhydryl group. The separation of the products was performed on a column with a pentafluorphenylpropyl stationary phase, allowing multiple mechanisms of selectivity. More than 50 peaks were separated in one run, reflecting the degree of dendrimer PEGylation (PEG average molecular mass: 3,000). Moreover, modification of PAMAM with a single alkyne group could be distinguished. The developed method can be used for the general characterization and separation of PAMAM derivatives, in which the degree of modification is critical for final applications.
In this study, we propose substrate-independent modification for creating a protein-repellent surface based on dopamine-melanin anchoring layer used for subsequent binding of poly(ethylene oxide) (PEO) from melt. We verified that the dopamine-melanin layer can be formed on literally any substrate and could serve as the anchoring layer for subsequent grafting of PEO chains. Grafting of PEO from melt in a temperature range 70-110 °C produces densely packed PEO layers showing exceptionally low protein adsorption when exposed to the whole blood serum or plasma. The PEO layers prepared from melt at 110 °C retained the protein repellent properties for as long as 10 days after their exposure to physiological-like conditions. The PEO-dopamine-melanin modification represents a simple and universal surface modification method for the preparation of protein repellent surfaces that could serve as a nonfouling background in various applications, such as optical biosensors and tissue engineering.
- MeSH
- Adsorption MeSH
- Coated Materials, Biocompatible analysis chemical synthesis MeSH
- Biosensing Techniques methods MeSH
- Hydrophobic and Hydrophilic Interactions MeSH
- Blood Proteins chemistry metabolism MeSH
- Humans MeSH
- Melanins chemistry MeSH
- Microscopy, Atomic Force MeSH
- Polyethylene Glycols chemistry MeSH
- Surface Properties MeSH
- Cattle MeSH
- Tissue Engineering methods MeSH
- Microscopy, Electron, Transmission MeSH
- Protein Binding MeSH
- Chromatography, High Pressure Liquid MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Cattle MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
