The modification of biomaterial surfaces has become increasingly relevant in the context of ongoing advancements in tissue engineering applications and the development of tissue-mimicking polymer materials. In this study, we investigated the layer-by-layer (LbL) deposition of polyelectrolyte multilayer protein reservoirs consisting of poly-l-lysine (PLL) and hyaluronic acid (HA) on the hydrophobic surface of poly(glycerol sebacate) (PGS) elastomer. Using the methods of isothermal titration calorimetry and surface plasmon resonance, we systematically investigated the interactions between the polyelectrolytes and evaluated the deposition process in real time, providing insight into the phenomena associated with film assembly. PLL/HA LbL films deposited on PGS showed an exceptional ability to incorporate bone morphogenetic protein-2 (BMP-2) compared to other growth factors tested, thus highlighting the potential of PLL/HA LbL films for osteoregenerative applications. The concentration of HA solution used for film assembly did not affect the thickness and topography of the (PLL/HA)10 films, but had a notable impact on the hydrophilicity of the PGS surface and the BMP-2 release kinetics. The release kinetics were successfully described using the Weibull model and hyperbolic tangent function, underscoring the potential of these less frequently used models to compare the protein release from LbL protein reservoirs.
- MeSH
- Hyaluronic Acid * chemistry MeSH
- Layer-by-Layer Nanoparticles MeSH
- Polyelectrolytes MeSH
- Polylysine * chemistry MeSH
- Polymers MeSH
- Publication type
- Journal Article MeSH
A novel polyelectrolyte nanocarrier was synthesized via layer-by-layer self-assembly of polycationic and polyanionic chains. The nanocarrier is composed of polyglutamate grafted chitosan core, dextran sulfate as a complexing agent, and polyethyleneimine shell decorated with folic acid. This polyelectrolyte complex has unique physicochemical properties so that the core is considered as an efficient carrier for LTX-315 and melittin peptides, and the shell is suitable for delivery of miR-34a. The spherical nanocarriers with an average size of 123 ± 5 nm and a zeta potential of -36 ± 1 mV demonstrated controlled-release of gene and peptides ensured a synergistic effect in establishing multiple cell death pathways on chemoresistance human breast adenocarcinoma cell line, MDA-MB-231. In vitro cell viability assays also revealed no cytotoxicity for the nanocarriers, and an IC50 of 15 μg/mL and 150 μg/mL for melittin and LTX-315, respectively, after 48 h, whereas co-delivery of melittin with miR-34a increased smart death induction by 54%.
- MeSH
- Cell Death MeSH
- Chitosan * MeSH
- Humans MeSH
- Melitten pharmacology MeSH
- MicroRNAs administration & dosage genetics MeSH
- Cell Line, Tumor MeSH
- Breast Neoplasms * drug therapy MeSH
- Nanoparticles * MeSH
- Oligopeptides MeSH
- Polyelectrolytes MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
The alkaline milieu of chronic wounds severely impairs the therapeutic effect of antibiotics, such as rifampicin; as such, the development of new drugs, or the smart delivery of existing drugs, is required. Herein, two innovative polyelectrolyte nanoparticles (PENs), composed of an amphiphilic chitosan core and a polycationic shell, were synthesized at alkaline pH, and in vitro performances were assessed by 1H NMR, elemental analysis, FT-IR, XRD, DSC, DLS, SEM, TEM, UV/Vis spectrophotometry, and HPLC. According to the results, the nanostructures exhibited different morphologies but similar physicochemical properties and release profiles. It was also hypothesized that the simultaneous use of the nanosystem and an antioxidant could be therapeutically beneficial. Therefore, the simultaneous effects of ascorbic acid and PENs were evaluated on the release profile and degradation of rifampicin, in which the results confirmed their synergistic protective effect at pH 8.5, as opposed to pH 7.4. Overall, this study highlighted the benefits of nanoparticulate development in the presence of antioxidants, at alkaline pH, as an efficient approach for decreasing rifampicin degradation.
- MeSH
- Calorimetry, Differential Scanning MeSH
- X-Ray Diffraction MeSH
- Hydrogen-Ion Concentration MeSH
- Drug Delivery Systems * MeSH
- Nanoparticles chemistry ultrastructure MeSH
- Polyelectrolytes chemistry MeSH
- Proton Magnetic Resonance Spectroscopy MeSH
- Rifampin pharmacology MeSH
- Dextran Sulfate chemistry MeSH
- Spectrophotometry, Ultraviolet MeSH
- Spectroscopy, Fourier Transform Infrared MeSH
- Static Electricity MeSH
- Drug Liberation MeSH
- Particle Size MeSH
- Chromatography, High Pressure Liquid MeSH
- Publication type
- Journal Article MeSH
Pancreatic ductal adenocarcinoma (PDAC) is a growing medical problem associated with extensive metastasis and high mortality. Intraperitoneal (IP) administration of therapeutics promises to help the treatment of cancers originated from organs in the peritoneal cavity. In this study, we evaluated how physicochemical properties of self-assembled polycation/siRNA nanoparticles affect their IP delivery efficacy in an orthotopic PDAC model. We have examined the effect of covalent polycation modification with lipophobic and hydrophobic tetrafluoro-p-toluic acid (TFTA), hydrophobic cholesterol, and hydrophilic poly(ethylene glycol) respectively. The surface charge of the three different nanoparticles was also modulated by coating the surface with serum albumin. We found that positively charged fluorine-containing particles with lipophobic properties based on a mixture of positively charged polymeric AMD3100 CXCR4 antagonist (PAMD) and PAMD modified with TFTA (mPAMD-TFTA)/siRNA displayed the best cell uptake and transfection efficacy in vitro. Biodistribution evaluation of the nanoparticles in a syngeneic orthotopic PDAC model revealed that the fluorine-containing formulation also achieved the highest PDAC tumor accumulation after IP administration. With a combination of CXCR4 inhibition by PAMD and PLK1 downregulation by siRNA, the treatment with mPAMD-TFTA/siPLK1 showed significant inhibition of both primary and metastatic PDAC tumors. Overall, our study provides insights into and guides the design of the nanoparticles for improved IP delivery of siRNA in PDAC.
- MeSH
- Halogenation * MeSH
- Humans MeSH
- RNA, Small Interfering MeSH
- Cell Line, Tumor MeSH
- Pancreatic Neoplasms * drug therapy MeSH
- Polyelectrolytes MeSH
- Tissue Distribution MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
A colloidal system able to act as a miniature reactor for on-demand release of reactive payloads has been demonstrated. The system is based on submicrometer aggregates consisting of anionic liposomes that act as storage reservoirs for the reactants, superparamagnetic iron oxide nanoparticles (SPIONs) that enable magnetic positioning in space and controlled release of reactants from the liposomes by radiofrequency stimulation, and an oppositely charged polyelectrolyte (poly-l-lysine) that keeps the constituent elements within the aggregates at a defined ratio. The kinetics of liposome-PLL-SPION heteroaggregation was systematically mapped and a suitable composition of the liposome bilayer was found such that the system exhibits stability at ambient conditions and radiofrequency triggered release at physiological temperature. The functionality of the system was demonstrated using a reaction between resazurin and ascorbic acid. The ability to release the reactants on-demand at defined time points was demonstrated. The system opens up opportunities for the controlled local delivery of unstable of highly bioactive molecules produced in situ and on demand from stable precursors.
The formation and properties of supported lipid bilayers (SLB) containing hydrophobic nanoparticles (NP) was studied in relation to underlying cushion obtained from selected polyelectrolyte multilayers. Lipid vesicles were formed from zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and negatively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) in phosphate buffer (PBS). As hydrophobic nanoparticles - quantum dots (QD) with size of 3.8nm (emission wavelength of 420nm) were used. Polyelectrolyte multilayers (PEM) were constructed by the sequential, i.e., layer-by-layer (LbL) adsorption of alternately charged polyelectrolytes from their solutions. Liposomes and Liposome-QDs complexes were studied with Transmission Cryo-Electron Microscopy (Cryo-TEM) to verify the quality of vesicles and the position of QD within lipid bilayer. Deposition of liposomes and liposomes with quantum dots on polyelectrolyte films was studied in situ using quartz crystal microbalance with dissipation (QCM-D) technique. The fluorescence emission spectra were analyzed for both: suspension of liposomes with nanoparticles and for supported lipid bilayers containing QD on PEM. It was demonstrated that quantum dots are located in the hydrophobic part of lipid bilayer. Moreover, we proved that such QD-modified liposomes formed supported lipid bilayers and their final structure depended on the type of underlying cushion.
- MeSH
- Cryoelectron Microscopy MeSH
- Phosphatidylcholines chemistry MeSH
- Phosphatidylethanolamines chemistry MeSH
- Phosphorylcholine chemistry MeSH
- Hydrophobic and Hydrophilic Interactions MeSH
- Quantum Dots * MeSH
- Lipid Bilayers chemistry MeSH
- Polyelectrolytes chemistry MeSH
- Publication type
- Journal Article MeSH
Synthesis of theranostic nanoparticles, which combine both therapeutic and diagnostic capabilities in one platform can be considered as a step forward personalized medicine, since it allows tracing the delivery of the drug to targeted organ. Thus, the aim of this work was to prepare gadolinium alginate gel nanoparticles (gadolinum nanogels - GdNG) by the reverse microemulsions and physical crosslinking method as the vehicles able to carry hydrophilic drugs and to be traced by the Magnetic Resonance Imaging (MRI). The average size of synthesized nanoparticles was about 110nm and the batch concentration was 10(10) particles/ml. The morphology of nanogeles was visualized by Cryo-Scanning Electron Microscopy. Surface of nanogels particles was modified by the Layer-by-Layer (LbL) technique using natural polyelectrolytes. The cytotoxicity of non-modified and LbL modified nanogels was evaluated by the cellular viability quantification and cell death assessments using MTT and LDH biochemical tests, respectively. We encapsulated the model compound - fluorescent dye (Rhodamine b) in nanogels networks and proved the possibility of GdNG visualization by MRI.
- MeSH
- Alginates chemistry MeSH
- Cell Death MeSH
- Fluorescent Dyes chemistry MeSH
- Gadolinium chemistry MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Cell Line, Tumor MeSH
- Polyethylene Glycols chemical synthesis chemistry MeSH
- Polyethyleneimine chemical synthesis chemistry MeSH
- Theranostic Nanomedicine * MeSH
- Cell Survival MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
We report on the physicochemical properties and self-assembly behavior of novel efficient pH-sensitive nanocontainers based on the Food and Drug Administration-approved anionic polymer Eudragit L100-55 (poly(methacrylic acid-co-ethyl acrylate) 1:1) and nonionic surfactant Brij98. The features of the interaction between Eudragit L100-55 and Brij98 at different pH values and their optimal ratio for nanoparticle formation were studied using isothermal titration calorimetry. The influence of the polymer-to-surfactant ratio on the size and structure of particles was studied at different pH values using dynamic light scattering and small-angle X-ray scattering methods. It was shown that stable nanoparticles are formed at acidic pH at polymer-to-surfactant molar ratios from 1:43 to 1:139. Trypsin was successfully encapsulated into Eudragit-Brij98 nanoparticles as a model bioactive component. The loading efficiency was determined by labeling trypsin with radioactive iodine-125. Eudragit-Brij98 nanoparticles effectively protected trypsin against pepsin digestion. The results showed that trypsin encapsulated into novel pH-sensitive nanocontainers retained more than 50% of its activity after treatment with pepsin compared with nonencapsulated trypsin. The described concept will contribute both to understanding the principles of and designing next-generation nanocontainers.
- MeSH
- Acrylic Resins chemistry MeSH
- X-Ray Diffraction MeSH
- Dynamic Light Scattering MeSH
- Hydrogen-Ion Concentration MeSH
- Scattering, Small Angle MeSH
- Nanoparticles chemistry MeSH
- Drug Carriers chemistry MeSH
- Plant Oils chemistry MeSH
- Polyelectrolytes chemistry MeSH
- Polyethylene Glycols chemistry MeSH
- Surface-Active Agents chemistry MeSH
- Iodine Radioisotopes MeSH
- Cattle MeSH
- Trypsin chemistry MeSH
- Particle Size MeSH
- Animals MeSH
- Check Tag
- Cattle MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Chitosan and chitosan-grafted polylactic acid as a matrix for BSA encapsulation in a nanoparticle structure were prepared through a polyelectrolyte complexation method with dextran sulfate. Polylactic acid was synthetized via a polycondensation reaction using the non-metal-based initiator methanesulfonic acid and grafted to the chitosan backbone by a coupling reaction, with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide as the condensing agent. The effect of concentration of the polymer matrix utilized herein on particle diameter, ζ-potential, encapsulation efficiency, and the release kinetic of the model protein bovine serum albumin at differing pH levels was investigated. The influence of pH and ionic strength on the behavior of the nanoparticles prepared was also researched. Results showed that grafting polylactic acid to chitosan chains reduced the initial burst effect in the kinetics of BSA release from the structure of the nanoparticles. Furthermore, a rise in encapsulation efficiency of the bovine serum albumin and diminishment in nanoparticle diameter were observed due to chitosan modification. The results suggest that both polymers actually show appreciable encapsulation efficiency; and release rate of BSA. CS-g-PLA is more suitable than unmodified CS as a carrier for controlled protein delivery.
- MeSH
- Chitosan chemistry MeSH
- Hydrogen-Ion Concentration MeSH
- Lactic Acid chemistry MeSH
- Delayed-Action Preparations MeSH
- Molecular Weight MeSH
- Nanoparticles chemistry MeSH
- Polymers chemistry MeSH
- Solubility MeSH
- Serum Albumin, Bovine chemistry MeSH
- Spectroscopy, Fourier Transform Infrared MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The high specific surface area and high reactivity of nanoscale zero-valent iron (nZVI) particles have led to much research on their application to environmental remediation. The reactivity of nZVI is affected by both the water chemistry and the properties of the particular type of nZVI particle used. We have investigated the reactivity of three types of commercially available Nanofer particles (from Nanoiron, s.r.o., Czech Republic) that are currently either used in, or proposed for use in full scale environmental remediation projects. The performance of one of these, the air-stable and thus easy-to-handle Nanofer Star particle, has not previously been reported. Experiments were carried out first in batch shaking reactors in order to derive maximum reactivity rates and provide a rapid estimate of the Nanofer particle's reactivity. The experiments were performed under near-natural environmental conditions with respect to the pH value of water and solute concentrations, and results were compared with those obtained using synthetic water. Thereafter, the polyelectrolyte-coated Nanofer 25S particles (having the highest potential for transport within porous media) were chosen for the experiments in column reactors, in order to elucidate nanoparticle reactivity under a more field-site realistic setting. Iopromide was rapidly dehalogenated by the investigated nZVI particles, following pseudo-first-order reaction kinetics that was independent of the experimental conditions. The specific surface area normalized reaction rate constant (kSA) value in the batch reactors ranged between 0.12 and 0.53Lm(-2)h(-1); it was highest for the uncoated Nanofer 25 particles, followed by the polyacrylic acid-coated Nanofer 25S and air-stable Nanofer Star particles. In the batch reactors all particles were less reactive in natural water than in synthetic water. The kSA values derived from the column reactor experiments were about 1000 times lower than those from the batch reactors, ranging between 2.6×10(-4) and 5.7×10(-4)Lm(-2)h(-1). Our results revealed that the easy-to-handle and air-stable Nanofer Star particles are the least reactive of all the Nanofer products tested. The reaction kinetics predicted by column experiments were more realistic than those predicted by batch experiments and these should therefore be used when designing a full-scale field application of nanomaterials for environmental remediation.
- MeSH
- Acrylic Resins chemistry MeSH
- Iohexol analogs & derivatives chemistry MeSH
- Kinetics MeSH
- Hydrogen-Ion Concentration MeSH
- Nanoparticles chemistry MeSH
- Porosity MeSH
- Environmental Restoration and Remediation MeSH
- Water chemistry MeSH
- Iron chemistry MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
