Generation Of Nanoparticles Research Articles

Overview on LNP-mRNA encapsulation unit operation: Mixing technologies, scalability, and influence of formulation & process parameters on physico-chemical characteristics.

Nanoparticles carrying active drug substances have been used since the 70's and have undergone numerous improvements since then. Nowadays, the latest generation of nanoparticles, called lipid nanoparticles (LNPs), is used for different applications such as vaccines and cancer treatments and offer a versatile approach to delivering genetic materials like RNA. LNPs are non-viral delivery vehicles obtained by the self-assembly of lipids during the rapid mixing of an aqueous phase containing mRNA with an organic phase containing lipids. During this process, mRNA is encapsulated within the LNP due to electrostatic interaction with an ionizable lipid. Different methods to produce LNPs are described in the literature and, as of now, continuous methods are mostly used to produce LNP-encapsulated mRNA (LNP-mRNA). T-shaped mixers are commonly used to produce mRNA-LNPs. This technology can operate at two different scales: microfluidic chips which can range from tens to hundreds of microns in size, and millimetric tubing for production scale up. This review intends to describe LNP-mRNA characteristics and their production modes with a special focus on the challenges related to the mixing quality, especially during scale-up.

Heyndrickxia coagulans spore-based nanoparticle generator for improved oral insulin delivery and hypoglycemic therapy.

Due to the two major physiological barriers restricted by mucus penetration and epithelia transport, oral insulin therapy using nano-delivery system remains challenging. Heyndrickxia coagulans spores can survive the harsh conditions of gastrointestinal tract (GIT), and penetrate in the mucus through germination to probiotics with their amphipathic proteinaceous coat shedding in the gut epithelium, which makes it possible to be functionalized with hydrophilic peptide/protein and form nanoparticles (NPs) in vivo. Inspired by the natural physiological properties of spores, novel deoxycholic acid-modified Heyndrickxia coagulans spores loaded with insulin (DA-Spore/Ins) as the generators of autonomous bio-based nanoparticles were designed to solve these absorption barriers to enhance oral insulin delivery. The DA-Spore/Ins delivery system achieved preferable drug protection and rapid mucus penetration through its germination in the intestinal microenvironment. Meanwhile, DA-Spore/Ins NPs could be spontaneously formed by the self-assembly of the disintegrated DA-covalently amphipathic protein coat and the hydrophilic protein/peptides drug. This can efficiently transport through the epithelial cells through the bile acid pathway. In vivo studies indicated that DA-Spore/Ins delivery system achieved an oral relative bioavailability of 15.1% and superior hypoglycemic effect in type I diabetic rats characterized by good biocompatibility. These studies suggested that the intrinsic biological characteristics of Heyndrickxia coagulans spore-based nanogenerators rendered their promising application in oral insulin or other protein drug therapy.

Soluplus Stabilized Amorphous Dispersions for Enhanced Oral Absorption of Felodipine.

Overcoming the poor aqueous solubility of small-molecule drugs is a major challenge in developing clinical pharmaceuticals. Felodipine (FLDP), an L-type calcium calcium channel blocker, is a poorly water-soluble drug. The study aimed to explore the potential applications of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (Soluplus) stabilized amorphous dispersions for augmenting the oral delivery of poorly water-soluble drugs. Soluplus-stabilized amorphous FLDP (FLDP-SSAs) was prepared using a two-phase mixing method. The samples were analyzed for their microscopic and macroscopic behavior using polarized light microscopy (PLM), differential scanning calorimetry (DSC), molecular simulation, and in vitro dissolution studies. Subsequently, the pharmacokinetics of FLDP-SSAs were evaluated. The maximum drug-to-Soluplus mass ratio of FLDP-SSAs was 50:50, with a drug concentration of 8.0 mg/mL. They exhibited an amorphous nature, as confirmed by PLM and DSC. FLDPSSAs generated nanoparticles with a particle size of approximately 50 nm during in vitro dissolution. Compared to FLDP oral solution, FLDP-SSAs exhibited higher solubility due to their amorphous nature and the generation of nanoparticles. The area under the curve (AUC) for oral FLDP-SSAs was 16.7-fold larger than that of the FLDP suspension. FLDP-SSAs could stabilize FLDP in an amorphous state and serve as drug carriers to enhance oral absorption.

Colloidal Protein–Silver Nanoparticle Metalloenzyme as Artificial Redox Biocatalyst

Efficient and sustainable catalytic processes are crucial for advancing green chemical manufacturing. Here, we describe the synthesis of novel silver artificial metalloenzymes in colloidal form in aqueous media and room temperature. The strategy is based on the in situ generation of silver nanoparticles by a genetically modified Geobacillus thermocatenulatus lipase (GTL) in the active site as an inducer and scaffold protein, producing an enzyme–Ag bioconjugate. Using a structural analysis of the formation of silver nanoparticles by XRD and UV spectra, we found the formation of Ag2O species with nanoparticles of around 11 nm average diameter size. Gel filtration chromatography demonstrated the presence of single protein molecules in the bioconjugates, although silver nanoparticles were initially formed by cysteine coordination in the active site but later were formed in other parts of the protein (five AgNPs per molecules, which is in concordance with the UV size). The enzyme structure was altered after nanoparticle formation and Ag-S interaction, which was observed in fluorescence analysis. This new enzyme showed reductive activity against p-nitrophenol to p-amino and a high conversion > 99% in the reduction of acetophenone to phenylethanol, although the enantioselective was quite moderate but higher in water that in the presence of co-solvents. Finally, oxidase-like activity was evaluated in the direct oxidation of phenylethanol to acetophenone in water, obtained at around a 23% yield of ketone after 60 h.

Computational study of conjugate heat transfer and entropy generation of hybrid nano-particles in an enclosure with solid block

Computational study of conjugate heat transfer and entropy generation of hybrid nano-particles in an enclosure with solid block

IR Pulsed Laser Ablation of Carbon Materials in High Vacuum

This work aimed to understand how the energy released by short laser pulses can produce different effects in carbon targets with different allotropic states. The IR pulse laser ablation, operating at 1064 nm wavelength, 3 ns pulse duration, and 100 mJ pulse energy, has been used to irradiate different types of carbon targets in a high vacuum. Graphite, highly oriented pyrolytic graphite, glassy carbon, active carbon, and vegetable carbon have exhibited different mass densities and have been laser irradiated. Time-of-flight (TOF) measurements have permitted the evince of the maximum carbon ion acceleration in the generated plasma (of about 200 eV per charge state) and the maximum yield emission (96 μg/pulse in the case of vegetal carbon) along the direction normal to the irradiated surface. The ion energy analyzer measured the carbon charge states (four) and their energy distributions. Further plasma investigations have been performed using a fast CCD camera image and surface profiles of the generated craters to calculate the angular emission and the ablation yield for each type of target. The effects as a function of the target carbon density and binding energy have been highlighted. Possible applications for the generation of thin films and carbon nanoparticles are discussed.

Synthesis of eco-friendly lipid-magnetite nanocomposite encapsulated Poinciana extract as promising insecticide against Culex pipiens

Mosquito-borne diseases represent a growing health challenge over time. Nanostructured lipid carriers (NLCs) are the second generation of solid lipid nanoparticles (SLNs), and they continue to attract significant interest as potential diagnostic and therapeutic tools in disease inhibition and insect control. Activated ingredients presented in the Poinciana leaves were extracted and GC–MS data indicated an increased abundance of terpenes, flavonoids, and phenolic substances. Poinciana extract was encapsulated to the vicinity of nanostructure lipid carrier, Po-NLC, and surface modified with magnetic nanoparticles, Po-NLC-MNPs. The synthesized nanoparticles depicted average particle size of 73.2 and 75.55 nm while zeta potential of (− 29.4) and (‒ 4.44 mV) for Po-NLC and Po-NLC-MNPs, respectively. Transmission electron microscope and morphology determination showed regular, irregular spherical and oval shapes with diverse single particle size. X-rays diffraction pattern of the freely synthesized MNPs was compared to the decorated NLC and the results manifested that the NLC was successfully decorated with MNPs. The larvicidal activity of plant extract, Poinciana extract (Po), and their nanoparticle conjugates against 3rd instar larvae of Culex pipiens was evaluated at 50, 100, 200, 500, 1000, and 1500 ppm concentrations. Both high and low concentrations of Po-NLC-MNPs, indicated potential larval mortality than plant extracts (Po extract) itself. The mortality rate reached 100% for 3rd instar larvae. Based on their relative toxicity, (Po-NLC-MNPs) was the best at killing larvae, followed by Po-NLC. The synthesized nps were checked for their cytotoxic effect against wi38 cell line. The in-vitro cytotoxicity results indicated that there was no significant cytotoxicity and the nanocomposite barely caused weak changes in the tested cells. The synthesized nanoparticles have potential to create a new generation of eco-friendly, effective alternatives for controlling mosquito-borne diseases.

Enhancing photovoltaic performance of monolithic dye-sensitized solar cells through green-synthesized CuO–FeO nanocomposite counter electrodes

To enhance monolithic dye-sensitized solar cell’s (MDSSC) photovoltaic performance, the nanoparticles and nanocomposite of green-synthesized copper oxide (CuO) and iron oxide (FeO) were effectively generated and inserted into nanoporous carbon counter electrode in this research. XRD studies carried out showed that the produced nanoparticles and nanocomposite were crystalline in nature. Furthermore, the possible chemical linkages that might be in charge of the nanoparticle generation were found using FTIR studies. Between 290 and 600 nm, the nanoparticles and nanocomposite showed optical absorption. Rod-like features were visible in the synthesized CuO–FeO nanocomposite's FE-SEM images. As a result, with 5.2% conversion efficiency, the CuO–FeO nanocomposite-based MDSSC performed better than any of the cells made using CuO and FeO nanoparticles alone.

Development of a Nano-toughened multifunctional composite hydrogel based on chitosan and its applications in catalytic and flexible sensors.

In this study, we developed a novel composite catalytic hydrogel, which integrates excellent mechanical properties, catalytic activity, and sensing performance. Discarded hydrogel sensors are reused as templates for in-situ generation of metal nanoparticles, and multifunctional hydrogels combining sensing and catalysis are realized. Polyacrylamide (PAM) provides a three-dimensional network structure, while octadecyl methacrylate (SMA) acts as a hydrophobic association center, enhancing the structural stability of the hydrogel. Dopamine coated with silica (PDA@SiO₂) nanoparticles act as nanoreinforcement points, further improving the mechanical strength of the hydrogel. Graphene(GN) imparts the hydrogel with good electrical conductivity and sensing capabilities. The hydrogel exhibits a strain of 1878 %, a tensile strength of 668 kPa, and toughness of 5615.2 kJ/m3, while also demonstrating excellent sensing performance, with gauge factor (GF) of 7.49 and response time of 168 ms, enabling a quick response to external strain. It effectively detects human motions, such as finger bending and joint movement. Additionally, PDA@SiO₂ acts as an active site for the synthesis of Ag NPs, facilitating the reduction of Rhodamine B at 25 °C with a catalytic rate constant of 0.504 min-1. After five catalytic cycles, the hydrogel retains over 99 % efficiency, demonstrating excellent cyclic stability and recyclability.

In-situ generation of hollow FeOx nanoparticles within electrospun N-doped carbon nanofibers for high-performance lithium storage

Iron-based oxides are deemed the most promising anode materials for lithium-ion batteries because of their low cost and high theoretical capacity; however, they still have disadvantages such as large volume variations and poor conductivity. To overcome these disadvantages, we successfully designed and fabricated a unique hollow Fe/Fe2O3 heterostructure nanospheres within N-doped CNFs hybrid structure through electrospinning and in situ oxidation. By adjusting the annealing temperature, the synergistic modulation of phase and morphology from solid Fe nanoparticles to hollow Fe/Fe2O3 and hollow Fe2O3 nanospheres was realized, which improved the electrochemical lithium storage performance. Benefiting from the unique hollow Fe/Fe2O3 heterostructural nanospheres and the hybridisation with the N-doped carbon nanofibers, the Fe/Fe2O3@NCNFs electrode exhibited higher lithium storage capacity, superior rate capability and outstanding cycle stability, achieving a reversible capacity of 938.2 mAh g−1 at 0.2 A g−1. Additionally, the Fe/Fe2O3@NCNFs electrode can still maintain a high capacity of 729.1 mAh g−1 after 900 cycles at a high current density of 0.5 A g−1, with a capacity retention of 97 %. Notably, this novel strategy can generally be applied to the design of different hollow nanostructured iron-based oxides, which is extremely important for developing advanced electrodes for use high-performance energy storage devices.

Hydride generation smartphone readable colorimetric system for speciation analysis of inorganic antimony without chromatographic separation

Antimony (Sb) was considered as a toxic metalloid element in environmental water system, the concentration of antimony in water sample was required to not be higher than 0.02 μg/mL. Miniaturized/portable analytical systems/devices were needed for on-site analysis of antimony. Herein, hydride generation was combined with a smartphone readable colorimetric method and used for the speciation analysis of inorganic antimony without chromatographic separation. Sb(III) was analyzed when masking reagent was used for Sb(V), total antimony concentration was obtained when Sb(V) was educed to Sb(III) before analysis. The conversion of Sb(Ⅲ) to SbH3 was achieved through hydride generation (HG) reaction, a redox reaction between SbH3 and HAuCl4 occurred with a result of in-situ generation of gold nanoparticles (Au NPs) on test paper, changing color from pale yellow to black and allowing for colorimetric analysis with naked-eye and smartphone RGB mode. Detectable limits of 0.02 μg/mL and 0.01 μg/mL can be recognized by naked-eye and smartphone mode, respectively. This miniaturized and easy-used smartphone readable analytical system was further used for on-site analysis of inorganic antimony in real samples, recoveries of 95–105 % were obtained.

Chitosan-based multimodal polymeric nanoparticles targeting pancreatic β-cells

Multimodal in vivo imaging of pancreatic islets might improve monitoring of endocrine grafts upon implantation, helping clinical validation of new regenerative therapies based on the replacement of β-cells in type 1 diabetes affected patients. Herein, the generation of chitosan-based multimodal diagnostic nanoparticles (NPs) able to target β-cells is described. The NPs, composed of chitosan (CH) and γ-poly-glutamic-acid (γ-PGA) with different “clickable” functional groups were chemoselectively decorated at the surface with Exendin-4 (Ex4), a ligand of glucagon-like peptide 1 (GLP-1) β-cell receptors, and with a DOTA containing linker, to chelate diagnostic radioisotopes. Furthermore, the NPs were conjugated with IRDye®800CW for multispectral optoacoustic tomography (MSOT). The affinity of Ex4 decorated NPs towards GLP-1R was confirmed by competitive flow cytometry tests. The detectability of the NPs labeled with IRDye®800CW and Ex4 in MSOT experiments was demonstrated. In vivo biodistribution of Ex4 decorated NPs labelled with Ga-68 was studied with positron emission tomography (PET) experiments in mice. Specific binding to GLP-1 receptor expressing tissue was demonstrated in autoradiography experiments, showing potential of the multimodal NPs for specifically targeting β-cells.

Debittering and antioxidant improvement of soy protein hydrolysates using curcumin as hydrophobic core.

Protein hydrolysates possess various bioactive functions (e.g. antioxidant), but their bitter taste is unacceptable to most consumers. In the present study, a novel approach for debittering was introduced, which involved the utilization of a hydrophobic compound, curcumin (Cur). Soy protein hydrolysates (SPH), prepared through alcalase hydrolysis, served as the research model for this investigation. It was found that bitter intensity of SPH was dominated by the hydrophobic amino acid residues, and the addition of Cur could remarkably reduce bitterness. The debittering mechanism is attributed to the direct binding of Cur to the exposed hydrophobic amino acid residues of SPH via hydrophobic interaction, thereby shielding the hydrophobic bitter groups and hindering their interaction with the bitter taste receptors. Moreover, this debittering strategy leads to the generation of stable nanoparticles with a Cur-core/SPH-shell architecture, which can significantly improve the antioxidant capacity of SPH compared to those using biomacromolecules for encapsulation. Using curcumin as a hydrophobic core is a facile and feasible strategy with bifunction of debittering as well as improving bioactive effect of SPH, which may extend its application in foods. © 2024 Society of Chemical Industry.

Property of Protection against Simultaneous Action between Atomic Oxygen Erosion and Ultraviolet Irradiation by MIL-53(Al) Coating.

Rapid development of coatings with resistance to the space irradiation environment of low Earth orbit (LEO), which benefits long-duration exploration missions in LEO, improves the challenging urgency of revealing the interaction between atomic oxygen (AO) erosion and ultraviolet (UV) irradiation. Here, we investigated the simultaneous action of AO erosion and UV irradiation using polyimide (PI) and MIL-53(Al)-coated PI, confirming a synergistic enhancement effect of 21.20 and 14.96% compared to that of AO erosion alone. The resistance to simultaneous action was verified by a more stable chemical state and lower erosion yield (E y = 4.386 × 10-25 cm3/atom, 12% of pristine PI). Through first-principles calculations, the resistance processes to AO erosion and UV irradiation involve the formation of inert oxides, maintaining an unchanged framework and widening the band gap due to microstructure transformation, respectively. Based on these, simultaneous action resistance was explained, in which the boundaries between nanoparticle generation during UV irradiation provided a pathway for AO erosion and probability for collision with the framework to reduce the kinetic energy of AO. This work puts forward the novel investigation of simultaneous action in LEO, confirms the application potential of MIL-53(Al), and offers a new idea to protect the spacecraft.

Selenium Hydride-Induced Oxidase-like Activity Inhibition of Amorphous/Crystalline Manganese Dioxide: Colorimetric Assay for Selenium Detection.

Hydride generation-based optical sensors have achieved on-site visual selenium (Se) determination with high anti-interference capability, yet they rely on the change of single-color intensity with a narrow linear dynamic range. Herein, we combined selenium hydride (H2Se)-induced activity inhibition of a manganese dioxide (MnO2) nanozyme with different degrees of 3,3',5,5'-tetramethylbenzidine (TMB) oxidation to realize sensitive multicolor visual detection of Se(IV). Due to its high oxidase-like (OXD-like) activity and sensitive response to H2Se, amorphous/crystalline manganese dioxide (ac-MnO2) was selected to form the headspace single droplet for microextraction and recognition. Via headspace redox reaction with H2Se, ac-MnO2 was reduced into low valence accompanied by in situ generation of Se nanoparticles, leading to the formation of a Se-MnOx aggregate. The experimental results and theoretical calculation indicated that, compared with MnO2, Se-MnOx had decreased active sites for adsorbing O2 to generate •O2-, resulting in the nanozyme activity inhibition that was totally dependent on Se(IV) concentration. The implementation of this strategy enabled accurate Se(IV) detection with a linear range from 10 to 600 μg L-1 and a limit of detection of 1.8 μg L-1. The portable smartphone-based detection for real sample analysis further demonstrated that this assay can be an easy, convenient, and intelligent tool for on-site selenium determination.

Magnetron Sputtering Formation of Germanium Nanoparticles for Electrochemical Lithium Intercalation.

In the drive towards increased lithium based battery capacity, germanium is an attractive material due to its very high lithium storage capacity, second only to silicon. The persistent down-side is the considerable embrittlement accompanying its remarkable volume expansion of close to 300 %. A proven method to accommodate for this lattice expansion is the reduction of the size towards the nanoscale at which the fracturing is prevented by "breathing". In this work we employed a novel magnetron sputtering gas aggregation nanoparticle generator to create unprecedented layers of well-defined germanium nanoparticles with sizes below 20 nm. The electrochemical lithium intercalation was monitored by a suite of techniques under which Raman spectroscopy, which provided clear evidence of the presence of lithium inside the germanium nanoparticles. Moreover, the degree of lattice order was measured and correlated to the initial phases of the lithium-germanium alloy. This was corroborated by electron diffraction and optical absorption spectroscopy, of which the latter provided a strong dielectric change upon lithium intercalation. This study of low lithium concentrations inside layers of well-defined and very small germanium nanoparticles, forms a new avenue towards significantly increasing the lithium battery capacity.

Effect of pH on radiation-induced synthesis of gold nanoparticles in solutions of poly(1-vinylimidazole)–AuIII complexes

Irradiation of an aqueous ethanol solution of poly(1-vinylimidazole) containing AuIII ions with X-rays leads to the generation of gold nanoparticles (AuNPs) with an average size determined by the pH value of the medium. The results obtained demonstrate a prominent example of the formation of stable ultrasmall AuNPs (<2 nm) at neutral pH.

Formation and agglomeration of nanoparticles and carbon debris in MnO2@C/GO

Carbon-loaded manganese dioxide (MnO2) nanoparticle materials have potential applications in energy storage and conversion, environmental and sensing applications. Carbon-coated MnO2 nanoparticles can avoid particle agglomeration. However, the process of forming MnO2 nanoparticles and carbon shells is unclear when carbon material is used as a carrier. In this work, the generation and convergence processes of nanoparticles and carbon debris were probed at bulk and monolayer levels using graphene oxide as carrier. And it is deduced that MnO2 nanoparticles first nucleate and aggregate at GO plane. As the size of the nanoparticles increases, the surrounding nanoparticles further aggregate. GO is etched during the formation of nanoparticles, resulting in the formation of carbon debris. Amorphous carbon shells are mainly formed by the aggregation of carbon debris. The MnO2@C/GO obtained was tested for H2O2 detection and showed superior H2O2 reduction properties.

Correction to: Synergistic enhancement of electrochemical performance in reversible solid oxide cells via deficiency-induced oxygen vacancy and nanoparticle generation

Correction to: Synergistic enhancement of electrochemical performance in reversible solid oxide cells via deficiency-induced oxygen vacancy and nanoparticle generation

Advanced X/γ-Ray-Shielding Materials Enabled by the In Situ Generation of Cerium-Tungsten Nanoparticles Within Regenerated Collagen Fibers.

Advanced X- and γ-ray-shielding materials are conventionally designed and fabricated via the uniform dispersion of high-Z elements into the substrate. These soluble high-Z elements considerably reduced the particle size of functional components; however, the as-obtained composites exhibited weak absorption region at 40-80keV and poor water resistance. To address these issues, such materials are fabricated by introducing cerium and tungsten into regenerated collagen fibers (RCFs) using a "dual impregnation-desolvation" strategy. The uniform dispersion of functional components is achieved via the in situ generation of cerium-tungsten nanoparticles (CeW NPs) under multiple impregnating and desolvating cycles; as a result, the CeW NPs achieved an ultrasmall particle size of 17.15nm. Benefiting from the ultrasmall particle size and uniform dispersion of CeW NPs, the fabricated CeW-RCF composites exhibit satisfactory X- and γ-ray-shielding capabilities with an ultrahigh mass attenuation coefficient (MAC) of 5.9cm2g-1 at 83keV, higher than that of lead plates. The CeW-RCF composites also exhibit outstanding mechanical strength, low density, and high air permeability, demonstrating their superior wearability. This work provides novel insights into the design and fabrication of advanced X- and γ-ray-shielding materials with high radiation-shielding performance and enhanced wearability.