Preparation Of Microspheres Research Articles

Improving and controlling the drug loading capacity of seven quinolones in minced fish matrix based on microfluidics

Traditional spiking methods for preparing matrix reference material of aquatic products is difficult to control the drug content in the matrix, especially one matrix containing multiple drugs. Minced fish is commonly used for the preparation of matrix reference materials in aquatic products, which is a relatively complex matrix with stickiness and difficult handling. Drug loading capacity is a key factor affecting the effectiveness of matrix reference materials. Here, we proposed a new spiking approach to improve the drug loading capacity of seven quinolones based on microfluidics, simultaneously. Fresh grass carp tissue underwent grinding, fine filtration, centrifugation and reconstituted in distilled water to form a liquid sample, which was subsequently mixed with a sodium alginate solution (1 %) at a ratio of 1:1.2. The mixed solution was supplemented with seven quinolones of equal concentration, followed by the preparation of uniform fish gel microspheres using microfluidic technology. The results indicated that the recoveries of seven quinolones ranged from 82.54 % to 114.17 %, demonstrating a significant improvement in the drug loading capacity of these quinolones compared to traditional methods. Moreover, the drug concentration in the matrix can be precisely controlled. A strong linear relationship was observed between the concentration of seven quinolones in the matrix and its initial concentration, which could serve as a reference for the development of other matrix reference materials.

Biocompatible sodium alginate–silk fibroin antibacterial microspheres from a microfluidic platform for infected wound repair

Micro/nano drug delivery systems can provide ideal controlled drug release. Microfluidic chip technology plays an important role in the preparation of microspheres. Sodium alginate (SA) has been used to prepare microspheres as drug carriers owing to its good biosafety and easy preparation. However, these microspheres lack antimicrobial activity and drug loading efficiency, which prevent their application for infected wound repair. Although silver nanoparticles (AgNPs) possess broad-spectrum antibiotic activity, liquid mixtures of AgNPs and SA are too unstable to fabricate drug-loaded microspheres using microfluidic chip technology. In this study, AgNPs were coated with silk fibroin (SF) and then dispersed in SA solution to fabricate antibacterial microspheres (denoted SA-SF-Ag) using microfluidic chip technology. SA-SF-Ag effectively inhibited the growth of microorganisms and gradually released AgNPs. Moreover, in vivo results showed that SA-SF-Ag promoted infected wound healing and angiogenesis by killing Pseudomonas aeruginosa on the surface of infected skin wounds of mouse models. This study offers a new method to integrate AgNPs into organic polymeric microspheres for the treatment of infected wounds.

Low-molecular-weight microspheres with soft-shell characteristics for remarkable signal enhancement in LOCI applications

Light-Activated Oxygen Channel Immunoassay (LOCI) is very attractive in immunoassay due to its advantages of simplicity, sensitivity and automation. The preparation of donor/acceptor beads (DBs/ABs) in LOCI is crucial to the detection sensitivity. In this study, microspheres with “hard core-soft shell” structure were prepared by stepwise dosing with a chain transfer agent (CTA), 2,4-diphenyl-4-methyl-1-pentene (a-MSD). The soft-shell structure facilitated the penetration of the photosensitizer into the microsphere and was encapsulated at the shell layer, thereby significantly improving the activity of singlet oxygen (1O2, λ< 200 nm) in LOCI. With the amount of a-MSD added increased to 20 wt%, the molecular weight of the microspheres decreased to 7235, and the loading of the photosensitizer in the microspheres could be as high as 80.6%, which enhanced the signal of LOCI detection by about 12.77 times. When the addition of a-MSD was 10 wt%, the optimal molecular weight and soft-shell structure were obtained, with the best signal-to-noise ratio (S/N) of 58.24. Compared with solid microspheres, the S/N was improved by about 4.22 times. These findings indicated that low-molecular-weight soft-shell microspheres have great potential in immune-medical applications, and the idea of soft-shell microspheres provides a new strategy for the preparation of immune-magnetic beads and immune-fluorescence microspheres.

Development of mucoadhesive microspheres for intranasal delivery of fluconazole as an alternative treatment of cryptococcal meningitis infection in patients with acquired immunodeficiency

Cryptococcal meningitis is a deadly disease with few treatment options. Its incidence is still high and closely linked to the HIV/AIDS epidemic. This study aimed to develop a mucoadhesive microsphere delivery system for fluconazole for the intranasal route. Microspheres of mucoadhesive fluconazole formulation variables such as different amounts of drug concentration and polymer concentration were prepared by a simple emulsion-crosslinking method.The prepared microspheres' surface was characterised by SEM (Scanning electron microscopy) and evaluated for particle size, entrapment efficiency, production yield, infrared spectroscopic study, in-vitro muco-adhesion, and in-vitro drug release. The results showed that formula 1 is the optimal mucoadhesive microsphere preparation, with a particle size of 56.375m, a spherical surface shape, an entrapment efficiency of 99.96%, and a greater mucoadhesive capability during 6-hour evaluation. Furthermore, wash-off examination revealed that the mucoadhesive ability of this delivery system has a long duration and may release the active material at the right time. The result of the researches suggesting that the formulation of mucoadhesive microspheres of fluconazole could be used to treat cryptococcal meningitis infection in HIV/AIDS patients.

Preparation of magnetic amphiphilic resin microspheres via the one-step polymerization method and extraction of four glucocorticoids for HPLC–MS analysis

Amphiphilic materials can be used for sample preparation of chromatography or mass spectrometry. Amphiphilic materials with magnetic properties in combination with magnetic suction devices allow for automated sample preparation. However, conventional synthesis methods are cumbersome and not suitable for the mass production of the material. In this study, a micro-suspension polymerization method was developed to synthesize magnetic amphiphilic resin microspheres (MARMs), providing new ideas for the preparation of amphiphilic microspheres. MARMs with particle sizes ranging from 3 to 6 μm were successfully prepared, with BET surface area up to 653.2 m2/g. A magnetic solid-phase extraction method based on MARM-5 was developed for the extraction of four glucocorticoids including Cortisone, Hydrocortisone, Cortodoxone, and Corticosterone. This method had a very short adsorption time of 0.5 min and a total extraction time of only 13 min. The limit of detection for the four glucocorticoids ranged from 0.22 to 0.82 ng/L. There was a good linear relationship between sample concentration and peak area in the range of 25∼500 ng/L. Relative recovery of 98 %∼108 % and internal standard normalized matrix effect factors of 95∼114 % were obtained, and the relative standard deviation was between 2.3 % and 6.3 %. The MARMs would be used as excellent solid extraction material for glucocorticoids.

Preparation and characterization of silver-carbon composite semitransparent hollow microspheres for surface-enhanced Raman scattering

In this work, silver-carbon composite semitransparent hollow spheres (Ag/HCSs) have been successfully synthesized via hydrothermal carbonization (HTC) with trioctylamine (TOA) as a stabilizer and soft template. Furthermore, silver-carbon composites with core-shell structure (Ag@CSs) and carbon films loaded with silver nanoparticles composites with lamellar structure (Ag/CFs) were prepared by adjusting the amount of TOA. The Ag/HCSs were composed of a matrix of ultrathin translucent hydrothermal hollow carbon microspheres with Ag nanoclusters embedded, and numbers of Ag@CSs inside and outside of the hollow carbon microspheres. We further investigated the growth mechanism and morphology evolution, on the basis of the properties of Ag and HCSs, explored the application of the Ag/HCSs for surface-enhanced Raman scattering (SERS). SERS activity was investigated using Rhodamine 6 G (R6G) and crystal violet (CV) as the SERS probe molecules. Ag/HCSs exhibit the best SERS performance among three products. The semitranslucent carbon shell, localized surface plasmon resonances of AgNPs and the effect of charge transfer arising from oxygen-containing moieties make the Ag/HCSs to exhibit good SERS performance, which may give a little inspiration to prepare novel SERS substrates.

Preparation of magnetic DTPA-modified chitosan composite microspheres for enhanced adsorption of Pb(II) from aqueous solution

In this study, magnetic DTPA-modified chitosan composite microspheres (MDCM) were prepared by reverse emulsion-double crosslinking method (carbodiimide followed by glutaraldehyde) for removal of Pb(II) from aqueous solution. The obtained magnetic adsorbents were characterized by FTIR, SEM, XRD, VSM, BET, and 13C NMR. The effects of the pH, contact time, initial concentration, and competitive metal cations (Na(I), Ca(II), or Mg(II)) on Pb(II) adsorption were investigated. The results revealed that MDCM exhibited high removal performance over a wide pH range and in the presence of competitive metal cations. The maximum adsorption capacity of MDCM for Pb(II) is 214.63 mg g−1 at pH 3, which is higher than most recently reported magnetic adsorbents. Adsorption kinetics and isotherms can be described by the pseudo-second-order model and Langmuir model, respectively. In addition, MDCM is easy to regenerate and can be reused five cycles with high adsorption capacity. Finally, the adsorption mechanism was further revealed by FTIR and XPS analysis. Overall, MDCM has practical application potential in removing Pb(II) from contaminated wastewater due to its high adsorption efficiency, good reusability, and convenient magnetic separation.

Preparation and characterization of Cr2AlC microspheres prepared by spray-drying granulation

Spray-drying granulation has been widely used to produce granules with good flowability due to its attractive features of low cost, high efficiency, and mass-production. In the present study, Cr2AlC MAX phase microspheres with particle sizes of 30–70 μm have been successfully prepared by spray-drying granulation. The main influencing factors of solid content in slurry and atomizer frequency on sphericity, size, and apparent and tap densities of spray-dried Cr2AlC microspheres were investigated under constant pumping pressure and drying temperature. By optimization of spray-drying conditions, Cr2AlC microspheres with good sphericity, flowability, and apparent and tap densities were achieved from a slurry with a solid content of 60 wt% at an atomization frequency of 280 Hz. It was found that atomization frequency and solid content in slurry influence the flowability of microspheres, while the solid content plays a major role in improving the apparent density and tap density. The microstructure and phase composition of Cr2AlC microspheres was characterized. The spray-dried Cr2AlC microspheres are promising feedstock powders for preparation of high-quality cold-sprayed Cr2AlC coatings.

Preparation of PLGA Microspheres Using the Non-Toxic Glycofurol as Polymer Solvent by a Modified Phase Inversion Methodology.

Poly(D,L-lactide-co-glycolide is a biodegradable copolymer that can release pharmaceuticals. These pharmaceuticals can provide local therapy and also avert the clinical issues that occur when a drug must be given continuously and/or automatically. However, the drawbacks of using poly(D,L-lactide-co-glycolide include the kinetics and duration of time of poly(D,L-lactide-co-glycolide drug release, the denaturing of the drug loaded drug, and the potential clinical side effects. These drawbacks are mainly caused by the volatile organic solvents needed to prepare poly(D,L-lactide-co-glycolide spheres. Using the non-toxic solvent glycofurol solvent instead of volatile organic solvents to construct poly(D,L-lactide-co-glycolide microspheres may deter the issues of using volatile organic solvents. Up to now, preparation of such glycofurol spheres has previously met with limited success. We constructed dexamethasone laden poly(D,L-lactide-co-glycolide microspheres utilizing glycofurol as the solvent within a modified phase inversion methodology. These prepared microspheres have a higher drug load and a lower rate of water diffusion. This prolongs drug release compared to dichloromethane constructed spheres. The glycofurol-generated spheres are also not toxic to target cells as is the case for dichloromethane-constructed spheres. Further, glycofurol-constructed spheres do not denature the dexamethasone molecule and have kinetics of drug release that are more clinically advantageous, including a lower drug burst and a prolonged drug release.

Biomimetic biphasic microsphere preparation based on the thermodynamic incompatibility of glycosaminoglycan with gelatin methacrylate for hair regeneration

Hair follicle (HF) tissue engineering is promising for hair loss treatment especially for androgenetic alopecia. Physiologically, the initiation of HF morphogenesis relies on the interactions between hair germ mesenchymal and epithelial layers. To simulate this intricate process, in this study, a co-flowing microfluidic-assisted technology was developed to produce dual aqueous microdroplets capturing growth factors and double-layer cells for subsequent use in hair regeneration. Microspheres, called G/HAD, were generated using glycosaminoglycan-based photo-crosslinkable biological macromolecule (HAD) shells and gelatin methacrylate (GelMA) cores to enclose mesenchymal cells (MSCs) and mouse epidermal cells (EPCs). The findings indicated that the glycosaminoglycan-based HAD shells display thermodynamic incompatibility with GelMA cores, resulting in the aqueous phase separation of G/HAD cell spheres. These G/HAD microspheres exhibited favorable characteristics, including sustained growth factor release and wet adhesion properties. After transplantation into the dorsal skin of BALB/c nude mice, G/HAD cell microspheres efficiently induced the regeneration of HFs. This approach enables the mass production of approximately 250 dual-layer microspheres per minute. Thus, this dual-layer microsphere fabrication method holds great potential in improving current hair regeneration techniques and can also be combined with other tissue engineering techniques for various regenerative purposes.

Cheap and efficient strategy for photocatalytic degradation of ionic liquids by La/Ce-codoped TiO2@PAM composites.

Ionic liquids are regarded as green solvents mainly due to their non-volatile and easy regeneration and recycling properties. However, ionic liquids have negative effects on the environment and human health, especially alkyl imidazole ionic liquids are more toxic than traditional organic solutions. Studies on the toxicology, ecotoxicology, and degradation of ionic liquids are rarely found in the literature. Here, we prepared the cheap La and Ce-codoped TiO2@PAM (polyacrylamide) composite microspheres with a simple procedure for the first time to degrade three kinds of imidazole ionic liquids with high efficiency. The experimental results show that the composite La (0.25%) and Ce (0.15%)-codoped TiO2@PAM composite microspheres with calcination temperature of 450 °C had a high photocatalytic activity for 1-butyl-3-methyl imidazolium hexafluorophosphate, 1-hexyl-3-methyl imidazolium hexafluorophosphate, and 1-octyl-3-methyl imidazolium hexafluorophosphate with the concentration of 10 mg/L. The photocatalysis degradation extent of the three ionic liquids is 97.4, 91.2, and 88.5% at 90 min. This work opened a new route for the simple preparation of cheap composite microspheres in the photocatalytic degradation of ionic liquids with a high efficiency.

Preparation of pH-responsive chitosan microspheres containing aminopeptidase and their application in accelerating cheese ripening

Microencapsulated enzymes have been found to effectively accelerate cheese ripening. However, microencapsulated enzyme release is difficult to control, often resulting in enzyme release during cheese processing and causing texture and flavor defects. This study aims to address this issue by developing aminopeptidase-loaded pH-responsive chitosan microspheres (A-CM) for precise enzyme release during cheese ripening. An aminopeptidase with an isoelectric point (pH 5.4) close to the pH value of cheese ripening was loaded on chitosan microspheres through electrostatic interaction. Turbidity titration measurements revealed that pH 6.5 was optimal for binding aminopeptidase and microspheres, affording the highest loading efficiency of 58.16%. Various characterization techniques, including scanning electron microscopy, energy-dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy confirmed the successful loading of aminopeptidase molecules on the chitosan microspheres. In vitro release experiments conducted during simulated cheese production demonstrated that aminopeptidase release from A-CM was pH responsive. The microspheres retained the enzyme during the coagulation and cheddaring processes (pH 5.5-6.5) and only released it after entering the cheese-ripening stage (pH 5.0-5.5). By loading aminopeptidase on chitosan microspheres, the loss rate of the enzyme in cheese whey was reduced by approximately 79%. Furthermore, compared with cheese without aminopeptidase and cheese with aminopeptidase added directly, the cheeses made with A-CM exhibited the highest proteolysis level and received superior sensory ratings for taste and smell. The content of key aroma substances, such as 2/3-methylbutanal and ethyl butyrate, in cheese with A-CM was more than 15 times higher than the others. This study provides an approach for accelerating cheese ripening through the use of microencapsulated enzymes.

High-Voltage Electrostatic Field Hydrogel Microsphere 3D Culture System Improves Viability and Liver-like Properties of HepG2 Cells.

Three-dimensional (3D) hepatocyte models have become a research hotspot for evaluating drug metabolism and hepatotoxicity. Compared to two-dimensional (2D) cultures, 3D cultures are better at mimicking the morphology and microenvironment of hepatocytes in vivo. However, commonly used 3D culture techniques are not suitable for high-throughput drug screening (HTS) due to their high cost, complex handling, and inability to simulate cell-extracellular matrix (ECM) interactions. This article describes a method for rapid and reproducible 3D cell cultures with ECM-cell interactions based on 3D culture instrumentation to provide more efficient HTS. We developed a microsphere preparation based on a high-voltage electrostatic (HVE) field and used sodium alginate- and collagen-based hydrogels as scaffolds for 3D cultures of HepG2 cells. The microsphere-generating device enables the rapid and reproducible preparation of bioactive hydrogel microspheres. This 3D culture system exhibited better cell viability, heterogeneity, and drug-metabolizing activity than 2D and other 3D culture models, and the long-term culture characteristics of this system make it suitable for predicting long-term liver toxicity. This system improves the overall applicability of HepG2 spheroids in safety assessment studies, and this simple and controllable high-throughput-compatible method shows potential for use in drug toxicity screening assays and mechanistic studies.

OPTIMIZATION AND CHARACTERIZATION OF MICROSPHERES OF BERBERINE HYDROCHLORIDE USING BOX-BEHNKEN DESIGN

Objective: The current work sought to optimize Berberine hydrochloride (BBH)-loaded microspheres by examining the link between design parameters and experimental results. Methods: BBH-loaded microspheres were prepared by using the water-in-oil emulsion cross-linking process and optimized with a three-factor, three-level Box-Behnken design (BBD). Grafted gum polyvinyl alcohol (PVA) ratio (w/w) (A), Revolutions per minute (RPM) (B), and Span 20 (%) (C) were independent variables. The dependent variables were Percent Entrapment Efficiency (% EE) (R1), Percent Drug Loading (% DL) (R2), and Particle Size (µm) (R3). The generated polynomial equations and response surface plots were used to relate the dependent and independent variables. Microscopic examination, %EE, and % DL were determined to evaluate the optimized formulation. Fourier transforms infrared (FT-IR) spectroscopy studies and stability studies of optimized formulation were also carried out. Results: The optimized formulation (FMS6) had a polymer content of 2% w/v [Grafted gum (36.96): PVA (63.04)], a span 20 (0.78 %), and a prepared at the speed of 1225.92 rpm. The observed responses were close to the improved formulation's predicted values. The particle size, % EE, and % DL were found to be 1.10 µm, 82.79% and 16.48%, respectively. FT-IR spectroscopy study indicated that the drug was entrapped in microspheres. Conclusion: BBD provides a systematic approach to optimize the BBH microsphere preparation process. Additionally, the stability study results confirmed that FMS6 is not only the ideal formulation but also stable, ensuring its suitability for practical applications.

Preparation of magnetic oil-based gel microspheres containing di(2-ethylhexyl)phosphoric acid for extraction of scandium ions at low concentrations in aqueous solutions

Extraction of low-concentration rare earths is one of the important paths for the sustainability of the rare earth industry. The research and development of materials suitable for the extraction of rare earth ions at low concentrations is of great significance. Currently, the application of solvent extraction in the rare earth production industry is highly mature. However, it is not economical to use it for the extraction of low concentration rare earths with problems of phase separation and organic phase loss. This work innovatively proposes to encapsulate the extractant and diluent in magnetic oleogel microspheres, which are obtained by solubilizing magnetic poly (phenyl divinylbenzene)(PS-DVB) microspheres with the extractant and diluent.. The magnetic PS-DVB microspheres of 3 ∼ 16 μm were prepared by suspension polymerisation, followed by encapsulation of di(2-ethylhexyl)phosphoric acid (D2EHPA) and dichloroethane in magnetic PS-DVB microspheres using emulsion swelling, and then magnetic oil-based gel microspheres containing D2EHPA with a particle size of 10 ∼ 32 μm were obtained. The magnetic oil-based gel microspheres containing D2EHPA consist of about 96 wt% liquid phase and about 4 wt% solid phase, with D2EHPA accounting for more than 4.19 wt%. The magnetic oil-based gel microspheres are very close to small oil droplets and are superparamagnetic. The magnetic oil-based gel microspheres containing D2EHPA could completely extract 60 ppm of scandium ions(Sc3+) under the conditions of O:A = 1:50,1:60,1:70, and the extraction equilibrium times were 6, 9 and 12 min, respectively. This extractant encapsulation scheme inherits the selectivity of traditional extractants while simultaneously preserving the advantages of rapid extraction by solvent extraction.

Preparation of microspheres with sustained ketoprofen release by electrospray for the treatment of aseptic inflammation.

The treatment of aseptic inflammation has always been a clinical challenge. At present, non-steroidal drug-loaded microspheres have been widely used in the treatment of aseptic inflammation due to their excellent injectable and sustained release capabilities. In this study, ketoprofen-loaded shellac microspheres (Keto-SLAC) were prepared by electrospray. Alterations of Keto-SLAC morphology was observed in response to changed shellac concentration in ethanol solution through electrospray. Further examination revealed that ketoprofen presented as amorphous solid dispersion in the shellac microspheres. Most importantly, it was also shown that ketoprofen can be slowly released from the shellac matrix for up to 3weeks. In vitro cell experiments verified that the microspheres had favorable cell compatibility. We therefore proposed that the prepared microspheres, being readily available in use in a variety of clinical settings through topical application, have promising therapeutic potential for the treatment of aseptic inflammation.

Preparation of Monodispersed Nanofibrous Gelatin Microspheres Using Homebuilt Microfluidics.

Gelatin, a protein derivative from collagen, is a versatile material with promising applications in tissue engineering. Among the various forms of gelatin scaffolds, nanofibrous gelatin microspheres (NFGMs) are attracting research efforts due to their fibrous nature and injectability. However, current methods for synthesizing nanofibrous gelatin microspheres (NFGMs) have limitations, such as wide size distributions and the use of toxic solvents. To address these challenges, the article introduces a novel approach. First, it describes the creation of a microfluidic device using readily available supplies. Subsequently, it outlines a unique process for producing monodispersed NFGMs through a combination of the microfluidic device and thermally induced phase separation (TIPS). This innovative method eliminates the need for sieving and the use of toxic solvents, making it a more ecofriendly and efficient alternative.

Preparation of polymer microspheres as oil displacement agent for extra-high temperature and extra-high salinity reservoirs

Based on the difficult problem that conventional polymer and gel can't be used for enhancing oil recovery in extra-high temperature (200 °C) and extra-high salinity (2 ×105 mg/L) reservoirs，an anti-temperature anti-salinity microspheres was prepared with 2,2′-bis[4-(4-aminophenoxy)phenyl] propane (BAPP), 3, 3′, 4, 4′-diphenyl ether dianhydride (ODPA) and phthalic anhydride (PA) as the monomers. The FTIR results showed that the temperature- and salt-resistant polyimide (PI) microspheres were prepared as target product. TGA showed that thermal decomposition of the unaged and aged PI-2 microspheres occurred over 281 °C and 252 °C, respectively; These values greatly exceed those of commercial HPAM, weak gel particles and pre-crosslinked gel particles. After the polyimide microspheres were aged for 120 d, the enhanced oil recovery of the PI-2 microspheres does not decrease significantly, so the long-term stability of two polyimide microspheres are very good at 200 °C and total dissolved solids (TDS) = 2 × 105 mg/L. The PI-2 microspheres had better properties than the conventional polymer and gel as profile control agent and water plugging agent. The microspheres possess the characteristics of being able to inject, block, and move, resulting in excellent oil displacement efficiency. The results of core displacement experiments revealed that PI-2 microspheres are highly efficient in oil displacement and have a strong ability to improve the water injection profile. Therefore, PI-2 microspheres can be used as an oil displacement agent in reservoirs with extremely high temperature and salt content.

Preparation of a cyclotriphosphazene microsphere bearing a phosphaphenanthrene structure towards fire-safety and mechanical enhancement for epoxy and its aramid fiber composite

The mismatch of flame retardancy and mechanical properties is still a challenge for developing high-performance epoxy resin (EP) and its aramid fiber (AF) composite.

Preparation of glassy carbon microspheres for use in electrochemical analysis

Preparation of glassy carbon microspheres for use in electrochemical analysis