Hydrodynamic Diameter Of Particles Research Articles

Solid Lipid Nanoparticles Based on Babassu Oil and Copaiba Oleoresin: A Promising Approach for Prostate Cancer Therapy.

Solid lipid nanoparticles (SLNs) represent promising nanostructures for drug delivery systems. This study successfully synthesized SLNs containing different proportions of babassu oil (BBS) and copaiba oleoresin (COPA) via the emulsification-ultrasonication method. Before SLN synthesis, the identification and quantification of methyl esters, such as lauric acid and β-caryophyllene, were performed via GC-MS analysis. These methyl esters were used as chemical markers and assisted in encapsulation efficiency experiments. A 22 factorial design with a center point was employed to assess the impact of stearic acid and Tween 80 on particle hydrodynamic diameter (HD) and polydispersity index (PDI). Additionally, the effects of temperature (8 ± 0.5 °C and 25 ± 1.0 °C) and time (0, 7, 15, 30, 40, and 60 days) on HD and PDI values were investigated. Zeta potential (ZP) measurements were utilized to evaluate nanoparticle stability, while transmission electron microscopy provided insights into the morphology and nanometric dimensions of the SLNs. The in vitro cytotoxic activity of the SLNs (10 µg/mL, 30 µg/mL, 40 µg/mL, and 80 µg/mL) was evaluated using the MTT assay with PC-3 and DU-145 prostate cancer cell lines. Results demonstrated that SLNs containing BBS and COPA in a 1:1 ratio exhibited a promising cytotoxic effect against prostate cancer cells, with a percentage of viable cells of 68.5% for PC-3 at a concentration of 30 µg/mL and 48% for DU-145 at a concentration of 80 µg/mL. These findings underscore the potential therapeutic applications of SLNs loaded with BBS and COPA for prostate cancer treatment.

Research of the properties of protein hydrolysates obtained from the broiler chicken gizzards as a potential component of bioactive film coatings

Protein hydrolysates are a promising active component in the production of bioactive film coatings for food products. Some biopolymers can exert the biological activity. More often, however, it is necessary to select biologically active substances to impart these properties to films. On the other hand, not all components allow forming films with the required properties, and therefore there is a need to study the individual technological characteristics of the components used. The purpose of the research is to establish the antioxidant and technological properties of protein hydrolysates obtained by microbial fermenta- tion of poultry by-products in whey with bifidobacteria, propionic acid bacteria and acidophilic bacteria as a potential basis for bioactive film coatings of food products. The hydrolysate obtained by fermentation without the addition of the specified bacterial species was used as a control sample. The functional properties of protein hydrolysates were assessed: antioxidant capacity by coulometric titration on an Expert-006 coulometer using ascorbic acid as a standard, antiradical activity by the DPPH method on a Jenway 6405 UV/Vis spectrophotometer with determination of the IC50 value. The technological proper- ties, solubility, water-holding, fat-holding and fat-emulsifying capacities were also determined by the gravimetric method. In addition, the average hydrodynamic diameter of particles in protein hydrolysates was determined using a Microtrac FLEX particle size analyzer. The results of studies of the antioxidant properties showed that the DPPH antiradical activity was 14.7% higher in the experimental samples of hydrolysates obtained by fermentation with bifidobacteria compared to the control; samples of hydrolysates obtained by fermentation with propionic acid bacteria showed an antioxidant capacity 29.6% higher than that of the control sample. The IC50 value turned out to be the highest in the control hydrolysate sample (2.994 mg/ml), which was 45.5–53.3% higher than that in the experimental hydrolysate samples. The results of determining the technologi- cal properties showed that they differ significantly for protein hydrolysates obtained by fermentation with different types of bacteria. For example, the highest values of fat-holding and fat-emulsifying capacities were found in the hydrolysate obtained by fermentation with bifidobacteria (351.1% and 61%, respectively), which shows its potential for incorporation into the bio- composite in the form of a protein-oil emulsion. The high solubility of the experimental samples of hydrolysates (from 90.1 to 91.4%) suggests their uniform distribution in the aqueous phase when composing the biocomposite of the film. Thus, the research results have shown the prospects of using protein hydrolysates from the gizzards of broiler chickens in whey as an active component of bioactive film coatings. The antioxidant properties of protein hydrolysates allow slowing down oxidative processes in the main food nutrients, which will contribute to an increase in the shelf life of food products packaged in bioac- tive films with this component.

Effect of Different Molecular Weight Hyaluronic Acids on Skim Milk Functional Properties.

Hyaluronic acid (HA), a naturally occurring polysaccharide with recognized health benefits, has gained approval for use in the food industry as a food additive, ingredient, and health supplement in numerous countries. HA can increase viscosity in solutions and is available commercially in various molecular weights (MW) depending on end applications. Nevertheless, no research has explored the impact of different MW HAs on functionality, rheological properties, and texture-building benefits in the dairy product matrix wherein they are incorporated. Therefore, the objective of this study was to evaluate how varying MWs of HA-specifically 8 kDa, 320 kDa, 980 kDa, and 2550 kDa at 0.25% (w/w) concentration-impact rheological characteristics, functional attributes, heat stability, protein stability, protein structure, and protein fractions within skim milk. The addition of HA led to an increase in the apparent viscosity of all samples. A higher G″ value over G' values for all HA samples was observed in frequency sweep, indicating the absence of interparticle interactions between HA particles. Protein stability and heat stability were significantly lower for 980 kDa and 2550 kDa HA as compared to the control and 8 kDa HA samples. As the MW increased, WHC, emulsion properties, and foaming stability notably increased. However, reversed results were found in the case of foaming activity. Moreover, no significant changes were observed in the percent area of individual protein fractions and the hydrodynamic diameter of protein particles. This study would help to understand the effect of HA when incorporated in dairy products for water binding or enhancement in viscosity-based applications.

Exploring the synergistic effects of goethite intercalated coal in the presence of humic acids for enhanced growth of Sinapis alba

BackgroundIron oxide mineral–humic complexes serve as a reservoir of bioavailable Fe for plants, releasing metal ligands and providing Fe–humic complexes directly usable by plant Fe-uptake mechanisms. In this study, we synthesized and characterized goethite α-FeOOH (G) nanoparticles (NPs) intercalated in coal (GC) to estimate the bioactivity effect of humic acids (HA). The synthesized GC NPs were characterized by X-ray diffraction, scanning electron microscopy (SEM), Mössbauer spectroscopy, N2 adsorption–desorption Brunauer–Emmett–Teller (BET) specific surface area, zeta potential, hydrodynamic particle diameter, iron ions release, and a phytoassay method of root elongation using the higher plant Sinapis alba.ResultsX-ray diffraction revealed that G was the primary phase in both GC and GC–HA complexes. Mössbauer spectroscopy analysis identified a goethite-doped Fe2+-in the GC samples. The intercalation of G into the coal matrix increased the specific surface area of GC, enhancing its HA sorption capacity. In addition, GC–HA demonstrated superior plant growth stimulation compared to HA and GC alone, indicating its role in colloidal stability. In contrast to GC, GC–HA exhibited a more consistent and time-dependent release of Fe3+ and Fe2+. This sustained Fe release from GC–HA, coupled with the formation of Fe3+ and more bioavailable (soluble) Fe2+ humic complexes is a promising result in terms of iron nanofertilizers production.ConclusionsThe use of goethite nanoparticles intercalated within a coal matrix and subsequently complexed with HA contributes to prolonged phytoactivity by employing slowly released nutrient additives within the coal mesoporous matrix.Graphical

Design and evaluation of nanoscale materials with programmed responsivity towards epigenetic enzymes.

Self-assembled materials capable of modulating their assembly properties in response to specific enzymes play a pivotal role in advancing 'intelligent' encapsulation platforms for biotechnological applications. Here, we introduce a previously unreported class of synthetic nanomaterials that programmatically interact with histone deacetylase (HDAC) as the triggering stimulus for disassembly. These nanomaterials consist of co-polypeptides comprising poly(acetyl L-lysine) and poly(ethylene glycol) blocks. Under neutral pH conditions, they self-assemble into particles. The hydrodynamic diameters of particles were typically withing the range of 108-190 nm, depending on degree of acetylation of the hydrophobic block. However, their stability is compromised upon exposure to HDACs, depending on enzyme concentration and exposure time. Our investigation, utilizing HDAC8 as the model enzyme, revealed that the primary mechanism behind disassembly involves a decrease in amphiphilicity within the block copolymer due to the deacetylation of lysine residues within the particles' hydrophobic domains. To elucidate the response mechanism, we encapsulated a fluorescent dye within these nanoparticles. Upon incubation with HDAC, the nanoparticle structure collapsed, leading to controlled release of the dye over time. Notably, this release was not triggered by denatured HDAC8, other proteolytic enzymes like trypsin, or the co-presence of HDAC8 and its inhibitor. We also demonstrated the biocompatibility and cellular effects of these materials in the context of drug delivery in different types of anticancer cell lines, such as MIA PaCa-2, PANC-1, cancer like stem cells (CSCs), and non-cancerous HPNE cells. We observed that the release of a model drug (such as a STAT3 pathway inhibitor, Napabucasin) can be loaded into these nanoparticles, with >90% of the dosage can be released over 3 h under the influence of HDAC8 enzyme in a controlled fashion. Further, we conducted a comprehensive computational study to unveil the possible interaction mechanism between enzymes and particles. By drawing parallels to the mechanism of naturally occurring histone proteins, this research represents a pioneering step toward developing functional materials capable of harnessing the activity of epigenetic enzymes such as HDACs.

Potencial aplicação da manteiga de munguba no desenvolvimento de sistemas nanoemulsionados

Abstract Munguba butter has bioactive compounds such as vitamin E and phytosterols, which has valued its application in the development of new products, with advantages in its use in emulsified formulations. Therefore, the objective was to develop and evaluate the stability of a nanoemulsion containing munguba butter as the oily phase. Munguba butter was extracted by the ultrasound assisted method and its HLB (hydrophilic-lipophilic balance) was determined. Next, formulations varying the concentration of butter from 1-40% were developed and classified into liquid or solid emulsion and phase separation. Liquid emulsions were evaluated for hydrodynamic particle diameter, polydispersity index (PDI), Zeta potential (ζ), rheological characterization, and stability assays. The butter had an HLB of 6.98. The NE 1.0% formulation was selected and demonstrated to be unstable at high temperatures (45 ± 2 °C) and remained stable at room temperature, refrigeration and light radiation for 90 days. Munguba butter, because it has high amounts of saturated fatty acids, hinders its application in the development of new products. However, the success in the development of the NE 1.0% formulation is noteworthy, remaining stable when exposed to refrigeration, room temperature and light radiation.

Efficient and Traceable Tamoxifen Delivery to Breast Cancer Cells Using Folic Acid‐Decorated and PEGylated Graphene Quantum Dots

AbstractGraphene quantum dots (GQDs) possess potential properties for the targeted transport and tracking of anticancer medication to tumor cells. For this purpose, the synthesized GQDs were decorated with folic acid (FA) and methoxy polyethylene glycol (mPEG2000), and finally loaded with tamoxifen (TMX) drug. The synthesized nano‐drug was characterized using FTIR, XRD, UV‐Vis, PL, HRTEM, FESEM, and DLS analytical devices. Based on the obtained data, the average hydrodynamic diameter of particles dissolved in water was 294.7 nm and the size of dehydrated particles was between 53 and 210 nm. PL data showed that prepared nanoparticles have an emission wavelength of 438 nm, which is in the blue fluorescent wavelength range, thus making these nanoparticles suitable for cell imaging. The encapsulation efficiency and loading percentage of tamoxifen in nanoparticles were calculated at about 52.5 % and 30 %, respectively, and cumulative drug release reached 89 % within 42 hours. The cytotoxicity effects of nanoparticles were investigated. According to IC50 results, the targeted mPEG‐GQDs‐FA/TMX (TMX‐FPGs) nano‐drug was more toxic than free TMX on MCF‐7 cells and had reduced side effects on healthy HDF cells. TMX‐FPGs induced apoptosis cell death, significantly. The confocal imaging experiments showed that TMX‐FPGs are appropriate for monitoring and targeting MCF‐7 cells.

Fucoidan as a carrier of antimicrobial peptide: Preparation and characterization of nisin-loaded particles

Fucoidan is an anionic sulphated polysaccharide found in brown seaweed. Due to its various biological activities, biodegradability, and biocompatibility, the application of fucoidan is increasing in various fields. The research was aimed to use fucoidan for nisin encapsulation. Nisin-loaded fucoidan particles were prepared by the complexation method in the pH range of 4.0–7.0. The interaction of nisin and fucoidan was confirmed by FT-IR spectroscopy, dynamic light scattering method, thermogravimetric and differential scanning calorimetry analysis. The stability of the particles was analysed under storage at 4 °C. After one month of storage, the hydrodynamic diameter and zeta potential of particles changed insignificantly. Encapsulated nisin preserved its biological activity. The antimicrobial activity was tested against Gram-positive bacteria Bacillus subtilis and Listeria innocua, and Gram-negative bacteria Escherichia coli and Salmonella typhimurium. Nisin-loaded-fucoidan particles exhibited antibacterial activity against Gram-positive bacteria B. subtilis and L. innocua comparable to free nisin. The application of fucoidan for the encapsulation of nisin is promising. A new nisin formulation could be used in the food industry for biopreservation.

(NaPO3)6-modulated reassembly of encapsulated curcumin nanoparticles from yolk granules: Preparation, characterization, and bioavailability

Our previous research has shown that yolk granules can act as a unitary carrier of lipophilic substances. In this study, the Ca2+ content was adjusted using (NaPO3)6 to control the reassembly of yolk granules for curcumin encapsulation to generate yolk granule-curcumin nanoparticles (Gra-Cur NPs). (NaPO3)6 reduced the particle hydrodynamic diameter (Dh). Dissociated granules had the same protein profile as untreated granules, indicating that no new protein subunits were produced. Hydrophobic interaction was the main force of curcumin binding to yolk granules, and curcumin is amorphous after encapsulated. Gra-Cur NPs had excellent thermal and storage stability. Flow cytometry revealed that the rate of HT-29 cell apoptosis and curcumin absorption of encapsulated curcumin was higher than that of curcumin dissolved in DMSO, with smaller Dh. The findings of this study will allow for the development and implementation of bioactive compounds as novel carriers.

Preparation of high permeability γ-Al2O3 ultrafiltration membranes from pseudo-boehmite industrial precursor

To obtain γ-Al2O3 ultrafiltration membranes, AlOOH sols which were usually derived from aluminum alkoxide were used as the top layer precursor. However, the colloidal sols obtained by this process were complex, high cost and time-consuming. Pseudo-boehmite, an industrial product with characteristics of high purity, excellent gelation and strong caking property, was widely used to prepare γ-Al2O3 products. In this work, mesoporous γ-Al2O3 ultrafiltration membranes were prepared conveniently and quickly by using pseudo-boehmite powder as precursor with colloidal sol-gel route at room temperature. The effects of H+/Al3+ molar ratio and polyvinyl alcohol (PVA) content on the properties of AlOOH sols and γ-Al2O3 ultrafiltration membranes were analyzed. Results showed that the viscosity and hydrodynamic particle diameter of the AlOOH sols can be controlled by changing the H+/Al3+ molar ratio, and the pore size of the prepared γ-Al2O3 ultrafiltration membranes could be varied by adjusting the PVA content in the AlOOH sols coating slurry. The pore size increased from 6.98 nm to 11.34 nm by increasing PVA content from 1.25% to 1.50%. Additionally, the γ-Al2O3 ultrafiltration membranes derived from the pseudo-boehmite exhibited a relatively high permeability (＞94.5 L m−2 h−1⋅MPa−1), which was higher than that of the aluminum alkoxide derived.

Fractionation of Aspen Wood to Produce Microcrystalline, Microfibrillated and Nanofibrillated Celluloses, Xylan and Ethanollignin.

A new method for extractive-catalytic fractionation of aspen wood to produce microcrystalline (MCC), microfibrillated (MFC), nanofibrilllated (NFC) celluloses, xylan, and ethanollignin is suggested in order to utilize all of the main components of wood biomass. Xylan is obtained with a yield of 10.2 wt.% via aqueous alkali extraction at room temperature. Ethanollignin was obtained with a yield of 11.2 wt.% via extraction with 60% ethanol from the xylan-free wood at 190 °C. The lignocellulose residue formed after the extraction of xylan and ethanollignin was subjected to catalytic peroxide delignification in the acetic acid-water medium at 100 °C in order to obtain microcrystalline cellulose. MCC is hydrolyzed with 56% sulfuric acid and treated with ultrasound to produce microfibrillated cellulose and nanofibrillated cellulose. The yields of MFC and NFC were 14.4 and 19.0 wt.%, respectively. The average hydrodynamic diameter of NFC particles was 36.6 nm, the crystallinity index was 0.86, and the average zeta-potential was 41.5 mV. The composition and structure of xylan, ethanollignin, cellulose product, MCC, MFC, and NFC obtained from aspen wood were characterized using elemental and chemical analysis, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) analyses, Gas chromatography (GC), Gel permeation-chromatography (GPC), Scanning electron microscopy (SEM), Atomic force microscopy (AFM), Dynamic light scattering (DLS), Thermal gravimetric analysis (TGA).

Hydrodynamic characterization of a vesicular stomatitis virus-based oncolytic virus using analytical ultracentrifugation.

Determination of the size, density, and mass of viral particles can provide valuable information to support process and formulation studies in clinical development. Analytical ultracentrifugation (AUC), as a first principal method, has been shown to be a beneficial tool for the characterization of the non-enveloped adeno associated virus (AAV). Here, we demonstrate the suitability of AUC for the challenging characterization of a representative for enveloped viruses, which usually are expected to exhibit higher dispersity than non-enveloped viruses. Specifically, the vesicular stomatitis virus (VSV)-based oncolytic virus VSV-GP was used to evaluate potential occurrence of non-ideal sedimentation by testing different rotor speeds and loading concentrations. The partial specific volume was determined via density gradients and density contrast experiments. Additionally, nanoparticle tracking analysis (NTA) was used to determine the hydrodynamic diameter of VSV-GP particles to calculate their molecular weight via the Svedberg equation. Overall, this study demonstrates the applicability of AUC and NTA for the characterization of size, density, and molar mass of an enveloped virus, namely VSV-GP.

COMPARATIVE CHARACTERIZATION OF AQUEOUS SUSPENSIONS OF MAGNETIC IRON OXIDE NANOPARTICLES WITH DIFFERENT PHASE COMPOSITIONS

The interaction of iron oxide nanoparticles with an aqueous medium has been studied. The composition of the nanoparticles corresponds to magnetite–maghemite solid solutions with different Fe2+/Fe3+ ratios. Nanoparticles that most closely correspond to the composition of maghemite (γ-Fe2O3) have largest hydrodynamic diameters and cause a drastic decrease in the pH of the dispersion medium during the dispersion of the powders in water. Nanoparticles that have a phase composition of a solid solution corresponding to the middle of the magnetite–maghemite series are characterized by a gradual and less pronounced decrease in pH. It has been shown that dilution of aqueous suspensions obtained from preliminarily dried powders within a concentration range of 100–0.001 mg/L followed by sonication leads to a significant increase in the hydrodynamic diameter of iron oxide particles. A possible mechanism of the studied interaction of nanoparticles with the aqueous medium has been considered. This mechanism comprises the hydration of Lewis acid sites formed by iron ions and changes in the character of the dissociation of hydroxyl groups depending on the pH of a suspension. The effect of surface passivation of the studied nanopowders with oleic acid on the processes under consideration has been investigated. The results obtained make it possible to predict the aggregative stability and a number of other characteristics of the studied suspensions being diluted with water.

Charged colloidal SiO2 dispersions in water and chloroform: Synthesis, properties and perspectives in dyes adsorption

The paper proposes a new method for the synthesis of ultradispersed amorphous SiO2 powders in the reverse emulsions stabilized by sodium bis-(2-ethylhexyl) sulfosuccinate (AOT). Colloidal dispersions of the powders were obtained by ultrasonication in water and chloroform. The number average effective hydrodynamic diameter of particles in the sols was 90 and 200 nm, and ζ-potential was − 68 ± 3 and 52 ± 7 mV for water and chloroform, respectively. Accountable for charge formation and transformation are the AOT molecules that were adsorbed on the SiO2 surface during the synthesis in АОТ emulsions. In water, АОТ– ions serve as the potential-determining ones, while Na+ ions act as the counterions that form the diffusion part of the electrical double layer. With a decrease in the solvent polarity, Na+ ions become the potential-determining ones, and АОТ– ions – the counterions. Thus, the АОТ molecules embedded into the hybrid SiO2 @ АОТ particle during the synthesis are a certain switch key of the particle surface potential. The transformation of the surface charge in dependence on polarity of the organic solvent makes it possible to apply the synthesized powders both as the cation- and anion-exchange sorbents for the recovery of dyes from aqueous and non-aqueous media. In terms of fundamental advances, the novelty of our work consists in extending the ion-exchange sorption mechanism of ionic dyes to the media with a low dielectric constant.

Extraordinary Destabilization of Silica Nanocolloids by Filtration

After silica nanoparticles in solutions were filtered by a syringe filter with a much larger pore size than the particle diameter Dp, the filtrated effects on the rapid coagulation rate in 1 M KCl solution, the dynamic light scattering diameter, and the zeta potential at pH ∼ 6 were investigated by employing the particles of two different sizes: S particles (Dp ∼ 50 nm) of silica and latex and L particles (Dp ∼ 300 nm) of silica. It was found that the hydrodynamic diameters of silica particles became a little smaller and the absolute values of their zeta potentials decreased significantly by filtration, but that is not the case for latex particles. As for the rapid coagulation rate, the value of silica S particles increased more than 2 orders of magnitude by filtration, but no significant difference was found in the case of silica L and latex S particles. From these data, it was postulated that the gel-like layer was removed from the surface of silica S particles by filtration and the existence of the gel-like layer resulted into about 2 orders of magnitude reduction of the rapid coagulation rate. The extraordinary reduction of rapid coagulation of silica particles at Dp < 150 nm was successfully estimated by the revised Smoluchowski theory, which we call the Higashitani-Mori (HM) model. It was also found that the rapid coagulation rate of filtrated particles decreased slowly with a decreasing particle size at Dp < ca. 250 nm, which was also estimated properly by the HM model, neglecting the contribution of the redispersion of coagulated particles. Another finding in this study was that the gel-like layers were recovered with time even if they were removed by filtration, although the detailed mechanism of this recovering is not known at present and left as a future problem.

Сонохимическое микроструктурирование альгината натрия для повышения его эффективности в технологии хлебобулочных изделий

Algae are a source of many biologically active compounds that can be used in food production to expand the range of functional products. For instance, sodium alginate possesses a complex of scientifically proven biologically active properties. In the food industry, it usually serves as a thickener, stabilizer, gelatio n agent, and water-retaining agent. The biological activity of this polysaccharide and its effect on the technological properties of food systems depend on the molecular weight and particle size uniformity. The present research objective was to study the method of sonochemical microstructuring of sodium alginate to increase its biological activity and efficiency as part of v arious bakery formulations.&#x0D; The research featured alginate gels, yeast suspensions of Saccharomyces cerevisiae, and bakery products. The sonochemical microstructuring of sodium alginate involved a low-frequency ultrasonic treatment at 240, 435, and 630 W/L and 50°C for 20, 25, and 30 min. The effect of the treatment included the following indicators: particle morphology vs. distribution of the hydrodynamic particle diameter in a dispersed medium, antioxidant activity, dynamic viscosity, in vitro bioactivity, and bioavailability against Paramecium caudatum and S. cerevisiae. The quality assessment of bakery products followed State Standard 58233-2018.&#x0D; The process of sonochemical microstructuring depolymerized large particles of sodium alginate into shorter ones: 5670 nm – 30.6%, 502 nm – 53.4%, 56.1 nm – 16%. It increased the antioxidant activity by 7 times and the potential in vitro bioactivity by 3.9%. The microstructured sodium alginate improved the fermentation activity of S. cerevisiae and reduced the yeast biomass by 8%. The resulting bakery products had a greater porosity by 5.9% and antioxidant activity by 3.7 times.&#x0D; The sonochemical microstructuring reduced the particle size of sodium alginate, as well as increased its biological activity. The sonochemically microstructured sodium alginate demonstrated a great potential for baked foods.

Defined Coadsorption of Prostate Cancer Targeting Ligands and PEG on Gold Nanoparticles for Significantly Reduced Protein Adsorption in Cell Media

A study on the surface chemistry of gold nanoparticles (AuNPs) utilizing gel electrophoresis is presented. The molecular design of targeting and stabilizing PEG ligands allows one to combine them in mixed ligand layers with control of relative composition. For all tested targeting and control ligands, coadsorption of PEG significantly reduces protein adsorption and matrix effects of cell media as compared to conjugates without PEG. Introducing carboxylic acid groups into the PEG ligand layer does not lead to increased protein adsorption as shown with carboxylic acid terminated PEG ligands. The controlled adsorption of PEG ligands with different molecular weights is used to disentangle the effects of particle charge and hydrodynamic diameter. Taken together, this study provides directions for the functionalization of nanoparticles to obtain conjugates which are well-defined in terms of composition and colloidally stable in complex media. This is in particular relevant for targeting applications and cell experiments.

Unaided efficient transglutaminase cross-linking of whey proteins strongly impacts the formation and structure of protein alginate particles

There is a dogma within whey protein modification, which dictates the necessity of pretreatment to enzymatic cross-linking of β-lactoglobulin (β-Lg). Here microbial transglutaminase (MTG) cross-linked whey proteins and β-Lg effectively in 50 mM NaHCO3, pH 8.5, without pretreatment. Cross-linked β-Lg spanned 18 to >240 kDa, where 6 of 9 glutamines reacted with 8 of 15 lysines. The initial isopeptide bond formation caused loss of β-Lg native structure with t1/2 = 3 h, while the polymerization occurred with t1/2 = 10 h. Further, cross-linking effects on protein carbohydrate interaction have been overlooked, leaving a gap in understanding of these complex food matrices. Complexation with alginate showed that β-Lg cross-linking decreased onset of particle formation, hydrodynamic diameter, stoichiometry (β-Lg/alginate) and dissociation constant. The complexation was favored at higher temperatures (40 °C), suggesting that hydrophobic interactions were important. Thus, β-Lg was cross-linked without pretreatment and the resulting polymers gave rise to altered complexation with alginate.

Orientational Dynamics of Magnetic Iron Oxide Nanoparticles in a Hydrogel: Observation by Magnetic Linear Dichroism under Oscillating Field.

For the success of biomedical applications of magnetic iron oxide nanoparticles (MION), such as magnetic hyperthermia and magnetic particle imaging, it is essential to understand the orientational dynamics of MION in a complex fluid under an alternating field. Here, using the magnetic linear dichroism (MLD) measurement, we directly observed the orientational behavior of MION in a hydrogel under a damped oscillating magnetic field (DOMF) of 33 kHz in frequency. Hydrophobically modified ethoxylated urethane (HEUR) is examined as the network polymer because the mesh size of the network is controllable with its concentration. We used two MIONs: a bare MION (MION1) and a MION coated with an amphiphilic polymer (MION2). Where the mesh size of the gel network is larger than the particle's hydrodynamic diameter, MION1 in the hydrogel rotates in the same manner in a simple solution, although the macroscopic rheological property of the medium is quite different. Meanwhile, the orientational behavior of MION2 is dramatically changed by the addition of HEUR molecules even below the minimum gelation concentration, indicating that MION2 is associated with the flower micelles of HEUR. By analyzing the MLD waveform, the orientational behavior of MION1 in the HEUR gel under a DOMF can be explained with single-mode relaxation, whereas that of MION2 is complicated; a rapid partial rotation near the particle and a whole slow rotation of the particle-flower micelle associate are superimposed. It is hard to distinguish this difference in orientational behaviors from the dynamic magnetization curve because the dominant magnetization reversal process is Néel rotation, the rotation of the magnetic moment in the particle. The MLD measurement is a potential tool for optimizing biomedical techniques utilizing MIONs and for nanorheology or colloid science in a complex matrix such as a hydrogel or cytoplasmic matrix.

Intra-articular injection of flavopiridol-loaded microparticles for treatment of post-traumatic osteoarthritis

Rapid joint clearance of small molecule drugs is the major limitation of current clinical approaches to osteoarthritis and its subtypes, including post-traumatic osteoarthritis (PTOA). Particulate systems such as nano/microtechnology could provide a potential avenue for improved joint retention of small molecule drugs. One drug of interest for PTOA treatment is flavopiridol, which inhibits cyclin-dependent kinase 9 (CDK9). Herein, polylactide-co-glycolide microparticles encapsulating flavopiridol were formulated, characterized, and evaluated as a strategy to mitigate PTOA-associated inflammation through the inhibition of CDK9. Characterization of the microparticles, including the drug loading, hydrodynamic diameter, stability, and release profile was performed. The mean hydrodynamic diameter of flavopiridol particles was ∼15 µm, indicating good syringeability and low potential for phagocytosis. The microparticles showed no cytotoxicity in-vitro, and drug activity was maintained after encapsulation, even after prolonged exposure to high temperatures (60 °C). Flavopiridol-loaded microparticles or blank (unloaded) microparticles were administered by intraarticular injection in a rat knee injury model of PTOA. We observed significant joint retention of flavopiridol microparticles compared to the soluble flavopiridol, confirming the sustained release behavior of the particles. Matrix metalloprotease (MMP) activity, an indicator of joint inflammation, was significantly reduced by flavopiridol microparticles 3 days post-injury. Histopathological analysis showed that flavopiridol microparticles reduced PTOA severity 28 days post-injury. Taken altogether, this work demonstrates a promising biomaterial platform for sustained small molecule drug delivery to the joint space as a therapeutic measure for post-traumatic osteoarthritis. Statement of significancePost-traumatic osteoarthritis (PTOA) begins with the deterioration of subchondral bone and cartilage after acute injuries. In spite of the prevalence of PTOA and its associated financial and psychological burdens, therapeutic measures remain elusive. A number of small molecule drugs are now under investigation to replace FDA-approved palliative measures, including cyclin-dependent kinase 9 (CDK9) inhibitors which work by targeting early inflammatory programming after injury. However, the short half-life of these drugs is a major hurdle to their success. Here, we show that biomaterial encapsulation of Flavopiridol (CDK9 inhibitor) in poly (lactic-co-glycolic acid) microparticles is a promising route for direct delivery and improved drug retention time in the knee joint. Moreover, administration of the flavopiridol microparticles reduced the severity of PTOA.