In this study, we synthesized magnetic graphene oxide nanoparticles functionalized with polyvinyl alcohol (GO-PVA-Fe3O4) for effective delivery of anticancer drug and its cytotoxic potential against human breast cancer cells MDAMB. Initially, GO was synthesized using a modified Hummer's method. Subsequently, the GO was functionalized with the biocompatible polymer PVA to enhance its aqueous stability and surface reactivity. Magnetic nanoparticles (Fe3O4) were then grafted onto the PVA-functionalized GO via a chemical co-precipitation method, resulting in the formation of a stable magnetic nanocomposite. The anticancer drug 5-fluorouracil (5FU) was loaded onto the surface of the nanocarrier by non-covalent interaction. The developed nanocomposite (GO-PVA-Fe3O4-5FU) showed high drug loading capacity of 14.17 % mg mg-1 along with pH-responsive drug release of anticancer drug 5FU. 5-FU has demonstrated around 30.40 % drug release which is about 2.5 times higher than the drug release at pH 7.4 that demonstrated improved and passive targeted drug release at cancer microenvironment. Cellular cytotoxicity of the developed nanocarrier with the drug showed biocompatibility and higher cytotoxicity against MDAMB with an IC50 value of 23.65 ± 3.72 µg/mL as compared to the nanocarrier without drug loading. Therefore, the obtained results demonstrate potential of the synthesized nanocarriers as effective platforms for drug delivery. Overall, the GO-based magnetic nanocomposites exhibited promising characteristics for passive targeted drug delivery applications, offering improved biocompatibility, pH-responsive controlled release, and suitability for prospective cancer therapeutics.
- Keywords
- 5FU, Anticancer, Cytotoxicity, Drug release, Magnetic graphene oxide,
- MeSH
- Fluorouracil * administration & dosage chemistry pharmacology MeSH
- Graphite * chemistry administration & dosage MeSH
- Hydrophobic and Hydrophilic Interactions MeSH
- Hydrogen-Ion Concentration MeSH
- Drug Delivery Systems MeSH
- Humans MeSH
- Magnetite Nanoparticles * chemistry MeSH
- Cell Line, Tumor MeSH
- Breast Neoplasms * drug therapy MeSH
- Nanocomposites * chemistry administration & dosage MeSH
- Drug Carriers chemistry MeSH
- Polyvinyl Alcohol chemistry MeSH
- Antimetabolites, Antineoplastic * administration & dosage chemistry MeSH
- Antineoplastic Agents * administration & dosage chemistry MeSH
- Drug Liberation MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Fluorouracil * MeSH
- Graphite * MeSH
- graphene oxide MeSH Browser
- Magnetite Nanoparticles * MeSH
- Drug Carriers MeSH
- Polyvinyl Alcohol MeSH
- Antimetabolites, Antineoplastic * MeSH
- Antineoplastic Agents * MeSH
Conventional Ag-decorated TiO2 coatings suffer from low adsorption capacity and burst release kinetics, limiting long-term antibacterial efficacy and risking cytotoxicity. An entirely different payload release approach can be based on metal-organic frameworks (MOFs), which offer tunable porosity, high surface area, and internal diffusion channels. Here, we report a thermally stabilized Ti-based MOF [NH2-MIL-125(Ti)] functionalized with Ag+ via reactive deposition, enabling high Ag loading (∼14.7 wt %) and sustained release. Annealing at 250 °C enhances aqueous stability, allowing diffusion-governed Ag+ delivery over >48 h, with 77% of the Ag still present in the MOF after a 24 h release. The system exhibits dose-dependent antibacterial activity in powders and comparable efficacy in coatings, with a more gradual release profile. This scalable platform is promising for long-acting coatings, wound interfaces, and implantable materials.
- Keywords
- NH2-MIL-125, antibacterial activity, metal−organic-frameworks (MOFs), silver,
- MeSH
- Anti-Bacterial Agents * chemistry pharmacology MeSH
- Escherichia coli drug effects MeSH
- Microbial Sensitivity Tests MeSH
- Metal-Organic Frameworks * chemistry MeSH
- Porosity MeSH
- Staphylococcus aureus drug effects MeSH
- Silver * chemistry pharmacology MeSH
- Titanium * chemistry MeSH
- Drug Liberation MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Anti-Bacterial Agents * MeSH
- Metal-Organic Frameworks * MeSH
- Silver * MeSH
- Titanium * MeSH
- titanium dioxide MeSH Browser
It is generally accepted that for safe use of neural interface electrodes, irreversible faradaic reactions should be avoided in favor of capacitive charge injection. However, in some cases, faradaic reactions can be desirable for controlling specific (electro)physiological outcomes or for biosensing purposes. This study aims to systematically map the basic faradaic reactions occurring at bioelectronic electrode interfaces. We analyze archetypical platinum-iridium (PtIr), the most commonly used electrode material in biomedical implants. By providing a detailed guide to these reactions and the factors that influence them, we offer a valuable resource for researchers seeking to suppress or exploit faradaic reactions in various electrode materials. We employed a combination of electrochemical techniques and direct quantification methods, including amperometric, potentiometric, and spectrophotometric assays, to measure O2, H2, pH, H2O2, Cl2/OCl-, and soluble platinum and iridium ions. We compared phosphate-buffered saline (PBS) with an unbuffered electrolyte and complex cell culture media containing proteins. Our results reveal that the "water window"─the potential range without significant water electrolysis─varies depending on the electrolyte used. In the culture medium that is rich with redox-active species, a window of potentials where no faradaic process occurs essentially does not exist. Under cathodic polarizations, significant pH increases (alkalization) were observed, while anodic water splitting competes with other processes in media, preventing prevalent acidification. We quantified the oxygen reduction reaction and accumulation of H2O2 as a byproduct. PtIr efficiently deoxygenates the electrolyte under low cathodic polarizations, generating local hypoxia. Under anodic polarizations, chloride oxidation competes with oxygen evolution, producing relatively high and cytotoxic concentrations of hypochlorite (OCl-) under certain conditions. These oxidative processes occur alongside PtIr dissolution through the formation of soluble salts. Our findings indicate that the conventional understanding of the water window is an oversimplification. Important faradaic reactions, such as oxygen reduction and chloride oxidation, occur within or near the edges of the water window. Furthermore, the definition of the water window significantly depends on the electrolyte composition, with PBS yielding different results compared with culture media.
- Keywords
- bioelectronics, electrochemistry, neurostimulation, platinum electrodes, reactive chlorine species, reactive oxygen species, water window,
- Publication type
- Journal Article MeSH
Chitosan is a promising adsorbent for removing a wide range of pollutants from wastewater. However, its practical application is hindered by instability in acidic environments, which significantly impairs its adsorption capacity and limits its utilization in water purification. While cross-linking can enhance the acid stability of chitosan, current solvent-based methods are often costly and environmentally unfriendly. In this study, a solvent-free mechanochemical process was developed using high-energy ball milling to cross-link chitosan with various polyanionic linkers, including dextran sulfate (DS), poly[4-styrenesulfonic acid-co-maleic acid] (PSSM), and tripolyphosphate (TPP). The mechanochemically cross-linked (MCCL) chitosan products exhibited superior adsorption capacity and stability in acidic solutions compared to pristine chitosan. Chitosan cross-linked with DS (Cht-DS) showed the highest Reactive Red 2 (RR2) adsorption capacity, reaching 1559 mg·g-1 at pH 3, followed by Cht-PSSM (1352 mg·g-1) and Cht-TPP (1074 mg·g-1). The stability of MCCL chitosan was visually confirmed by the negligible mass loss of Cht-DS and Cht-PSSM tablets in pH 3 solution, unlike the complete dissolution of the pristine chitosan tablet. The MCCL significantly increased the microhardness of chitosan, with the order Cht-DS > Cht-PSSM > Cht-TPP, consistent with the RR2 adsorption capacity. When tested on simulated rinsing wastewater from chromium electroplating, Cht-DS effectively removed Cr(VI) (98.75% removal) and three per- and polyfluoroalkyl substances (87.40-95.87% removal), following pseudo-second-order adsorption kinetics. This study demonstrates the potential of the cost-effective and scalable MCCL approach to produce chitosan-based adsorbents with enhanced stability, mechanical strength, and adsorption performance for treating highly acidic industrial wastewater containing a mixture of toxic pollutants.
- Keywords
- PFAS, adsorption, chitosan, cross-linking, mechanochemical synthesis,
- Publication type
- Journal Article MeSH
Extensive research has been conducted on the competitive adsorption of arsenate (AsO43-) and phosphate (PO43-) to mineral surfaces, but the stability of ferric arsenate mineral(oid)s under elevated phosphate levels remains poorly understood. Therefore, we investigated the impact of dissolved phosphate (0, 0.5, 50 mM) on the stability of amorphous ferric arsenate (AFA; FeAsO4·nH2O) and nano-crystalline yukonite [Ca2Fe3(AsO4)3(OH)4·4H2O], both synthetic and contained in natural As-contaminated soil (∼16 g/kg As) and mine-waste material (∼39 g/kg As) for up to one year. Substantial amounts of As (∼45% of total As) were released into solution from AFA and yukonite at high phosphate concentrations due to incongruent dissolution of the solids and substitution of arsenate by phosphate in both mineral(oids). After one year, both solids sequestered ∼8 wt% P with approximately 20-30% accounting for adsorbed and precipitated species. This P increase was also observed in the soil and mine-waste samples, where AFA and yukonite comprised up to 4.3 and 4.9 wt% P, respectively. The high reactivity of ferric arsenates with aqueous phosphate may lead to a substantial overestimation of adsorbed As determined by sequential As extractions of materials containing these phases and requires increased caution when applying phosphate to stabilize polymetallic mine wastes. Furthermore, long-term phosphate additions via fertilization of As-contaminated soil or renaturalized mine tailings containing amorphous or nano-crystalline ferric arsenates should be reduced to limit the export of As(V) into surface streams and groundwater.
- Keywords
- Adsorption, Amorphous ferric arsenate, Mobility, Phosphate, Precipitation, Substitution, Yukonite,
- Publication type
- Journal Article MeSH
C4AF is considered the least reactive main clinker phase, but its reactivity may be affected by adding supplementary cementitious materials (SCMs). Pure C4AF was synthesised in a laboratory furnace, and the role of silica fume without gypsum on its early hydration properties was monitored. Burning was carried out in four stages to achieve 99% purity of C4AF. Heat flow development was monitored by isothermal calorimetry over 7 days of hydration at 20°C and 40°C. The role of silica fume on hydrogarnet phase katoite (Ca3Al2(SiO4)3 - x(OH)4 x x = 1.5-3) formation during early hydration was studied. Rapid dissolution of C4AF, formation of metastable C-(A,F)-H and its conversion to C3(A, F)H6 was evidenced by isothermal calorimetry as a large exotherm. Changes in microstructure during early hydration were documented by SE micrographs, EDS point analyses, X-ray mapping and line scans by SEM-EDS. The phase composition was characterised by DTA-TGA and QXRD after 7 days of hydration. The katoite diffraction pattern is similar for the reference sample and sample with silica fume, but substitution in its structure can be revealed by X-ray microanalyses. The composition of katoite is variable due to the various extent of substitution of 4OH- by SiO4 4- due to silica fume.
- Keywords
- C4AF, hydration, katoite, microstructure, silica fume,
- Publication type
- Journal Article MeSH
The application of polymer-based drug delivery systems is advantageous for improved pharmacokinetics, controlled drug release, and decreased side effects of therapeutics for inflammatory disease. Herein, we describe the synthesis and characterization of linear N-(2-hydroxypropyl)methacrylamide-based polymer conjugates designed for controlled release of the anti-inflammatory drug dexamethasone through pH-sensitive bonds. The tailored release rates were achieved by modifying DEX with four oxo-acids introducing reactive oxo groups to the DEX derivatives. Refinement of reaction conditions yielded four well-defined polymer conjugates with varied release profiles which were more pronounced at the lower pH in cell lysosomes. In vitro evaluations in murine peritoneal macrophages, human synovial fibroblasts, and human peripheral blood mononuclear cells demonstrated that neither drug derivatization nor polymer conjugation affected cytotoxicity or anti-inflammatory properties. Subsequent in vivo tests using a murine arthritis model validated the superior anti-inflammatory efficacy of the prepared DEX-bearing conjugates with lower release rates. These nanomedicines showed much higher therapeutic activity compared to the faster release systems or DEX itself.
- Keywords
- Controlled drug release, Dexamethasone, HPMA, Hydrazone bond, Polymer conjugates,
- MeSH
- Anti-Inflammatory Agents therapeutic use MeSH
- Dexamethasone MeSH
- Doxorubicin chemistry MeSH
- Leukocytes, Mononuclear * MeSH
- Humans MeSH
- Mice MeSH
- Nanomedicine MeSH
- Drug Carriers chemistry MeSH
- Polymers chemistry MeSH
- Rheumatic Diseases * MeSH
- Drug Liberation MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Anti-Inflammatory Agents MeSH
- Dexamethasone MeSH
- Doxorubicin MeSH
- Drug Carriers MeSH
- Polymers MeSH
Long-acting injectable formulations represent a rapidly emerging category of drug delivery systems that offer several advantages compared to orally administered medicines. Rather than having to frequently swallow tablets, the medication is administered to the patient by intramuscular or subcutaneous injection of a nanoparticle suspension that forms a local depot from which the drug is steadily released over a period of several weeks or months. The benefits of this approach include improved medication compliance, reduced fluctuations of drug plasma level, or the suppression of gastrointestinal tract irritation. The mechanism of drug release from injectable depot systems is complex, and there is a lack of models that would enable quantitative parametrisation of the process. In this work, an experimental and computational study of drug release from a long-acting injectable depot system is reported. A population balance model of prodrug dissolution from asuspension with specific particle size distribution has been coupled with the kinetics of prodrug hydrolysis to its parent drug and validated using in vitro experimental data obtained from an accelerated reactive dissolution test. Using the developed model, it is possible to predict the sensitivity of drug release profiles to the initial concentration and particle size distribution of the prodrug suspension, and subsequently simulate various drug dosing scenarios. Parametric analysis of the system has identified the boundaries of reaction- and dissolution-limited drug release regimes, and the conditions for the existence of a quasi-steady state. This knowledge is crucial for the rational design of drug formulations in terms of particle size distribution, concentration and intended duration of drug release.
- Keywords
- Hydrolysis, Injectable depot systems, Nanosuspension, Paliperidone palmitate, Particle size distribution, Reactive dissolution,
- MeSH
- Antipsychotic Agents * MeSH
- Injections, Intramuscular MeSH
- Delayed-Action Preparations MeSH
- Humans MeSH
- Prodrugs * MeSH
- Solubility MeSH
- Suspensions MeSH
- Drug Liberation MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Antipsychotic Agents * MeSH
- Delayed-Action Preparations MeSH
- Prodrugs * MeSH
- Suspensions MeSH
Manganese oxides are considered an essential component of natural geochemical barriers due to their redox and sorptive reactivity towards essential and potentially toxic trace elements. Despite the perception that they are in a relatively stable phase, microorganisms can actively alter the prevailing conditions in their microenvironment and initiate the dissolution of minerals, a process that is governed by various direct (enzymatic) or indirect mechanisms. Microorganisms are also capable of precipitating the bioavailable manganese ions via redox transformations into biogenic minerals, including manganese oxides (e.g., low-crystalline birnessite) or oxalates. Microbially mediated transformation influences the (bio)geochemistry of manganese and also the environmental chemistry of elements intimately associated with its oxides. Therefore, the biodeterioration of manganese-bearing phases and the subsequent biologically induced precipitation of new biogenic minerals may inevitably and severely impact the environment. This review highlights and discusses the role of microbially induced or catalyzed processes that affect the transformation of manganese oxides in the environment as relevant to the function of geochemical barriers.
- Keywords
- biotransformation, manganese, manganese oxides, microorganisms, sorption,
- MeSH
- Manganese * chemistry MeSH
- Minerals chemistry MeSH
- Oxidation-Reduction MeSH
- Oxides * chemistry MeSH
- Manganese Compounds chemistry MeSH
- Environment MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Manganese * MeSH
- manganese oxide MeSH Browser
- Minerals MeSH
- Oxides * MeSH
- Manganese Compounds MeSH
Upconverting nanoparticles (UCNPs) are of particular interest in nanomedicine for in vivo deep-tissue optical cancer bioimaging due to their efficient cellular uptake dependent on polymer coating. In this study, particles, ca. 25 nm in diameter, were prepared by a high-temperature coprecipitation of lanthanide chlorides. To ensure optimal dispersion of UCNPs in aqueous milieu, they were coated with three different polymers containing reactive groups, i.e., poly(ethylene glycol)-alendronate (PEG-Ale), poly(N,N-dimethylacrylamide-co-2-aminoethylacrylamide)-alendronate (PDMA-Ale), and poly(methyl vinyl ether-co-maleic acid) (PMVEMA). All the particles were characterized by TEM, DLS, FTIR, and spectrofluorometer to determine the morphology, hydrodynamic size and ξ-potential, composition, and upconversion luminescence. The degradability/dissolution of UCNPs in water, PBS, DMEM, or artificial lysosomal fluid (ALF) was evaluated using an ion-selective electrochemical method and UV-Vis spectroscopy. The dissolution that was more pronounced in PBS at elevated temperatures was decelerated by polymer coatings. The dissolution in DMEM was relatively small, but much more pronounced in ALF. PMVEMA with multiple anchoring groups provided better protection against particle dissolution in PBS than PEG-Ale and PDMA-Ale polymers containing only one reactive group. However, the cytotoxicity of the particles depended not only on their ability to rapidly degrade, but also on the type of coating. According to MTT, neat UCNPs and UCNP@PMVEMA were toxic for both rat cells (C6) and rat mesenchymal stem cells (rMSCs), which was in contrast to the UCNP@Ale-PDMA particles that were biocompatible. On the other hand, both the cytotoxicity and uptake of the UCNP@Ale-PEG particles by C6 and rMSCs were low, according to MTT assay and ICP-MS, respectively. This was confirmed by a confocal microscopy, where the neat UCNPs were preferentially internalized by both cell types, followed by the UCNP@PMVEMA, UCNP@Ale-PDMA, and UCNP@Ale-PEG particles. This study provides guidance for the selection of a suitable nanoparticle coating with respect to future biomedical applications where specific behaviors (extracellular deposition vs. cell internalization) are expected.
- Keywords
- degradation, lanthanides, luminescence, nanoparticles, upconversion,
- MeSH
- Alendronate MeSH
- Rats MeSH
- Nanoparticles * chemistry MeSH
- Polyethylene Glycols chemistry MeSH
- Polymers * chemistry MeSH
- Water MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Alendronate MeSH
- Polyethylene Glycols MeSH
- Polymers * MeSH
- Water MeSH