Optimizing Process Parameters for Controlled Drug Delivery: A Quality by Design (QbD) Approach in Naltrexone Microspheres.

The formulation of microspheres involves a complex manufacturing process with multiple steps. Identifying the appropriate process parameters to achieve the desired quality attributes poses a significant challenge. This study aims to optimize the critical process parameters (CPPs) involved in the preparation of naltrexone microspheres using a Quality by Design (QbD) methodology. Additionally, the research aims to assess the drug release profiles of these microspheres under both in vivo and in vitro conditions. Critical process parameters (CPPs) and critical quality attributes (CQAs) were identified, and a Box-Behnken design was utilized to delineate the design space, ensuring alignment with the desired Quality Target Product Profile (QTPP). The investigated CPPs comprised polymer concentration, aqueous phase ratio to organic phase ratio, and quench volume. The microspheres were fabricated using the oil-in-water emulsion solvent extraction technique. Analysis revealed that increased polymer concentration was correlated with decreased particle size, reduced quench volume resulted in decreased burst release, and a heightened aqueous phase ratio to organic phase ratio improved drug entrapment. Upon analyzing the results, an optimal formulation was determined. In conclusion, the study conducted in vivo drug release testing on both the commercially available innovator product and the optimized test product utilizing an animal model. The integration of in vitro dissolution data with in vivo assessments presents a holistic understanding of drug release dynamics. The QbD approach-based optimization of CPPs furnishes informed guidance for the development of generic pharmaceutical formulations.

Effects of phantom microstructure on their optical properties.

Significance: Developing stable, robust, and affordable tissue-mimicking phantoms is a prerequisite for any new clinical application within biomedical optics. To this end, a thorough understanding of the phantom structure and optical properties is paramount. Aim: We characterized the structural and optical properties of PlatSil SiliGlass phantoms using experimental and numerical approaches to examine the effects of phantom microstructure on their overall optical properties. Approach: We employed scanning electron microscope (SEM), hyperspectral imaging (HSI), and spectroscopy in combination with Mie theory modeling and inverse Monte Carlo to investigate the relationship between phantom constituent and overall phantom optical properties. Results: SEM revealed that microspheres had a broad range of sizes with average (13.47±5.98) µm and were also aggregated, which may affect overall optical properties and warrants careful preparation to minimize these effects. Spectroscopy was used to measure pigment and SiliGlass absorption coefficient in the VIS-NIR range. Size distribution was used to calculate scattering coefficients and observe the impact of phantom microstructure on scattering properties. The results were surmised in an inverse problem solution that enabled absolute determination of component volume fractions that agree with values obtained during preparation and explained experimentally observed spectral features. HSI microscopy revealed pronounced single-scattering effects that agree with single-scattering events. Conclusions: We show that knowledge of phantom microstructure enables absolute measurements of phantom constitution without prior calibration. Further, we show a connection across different length scales where knowledge of precise phantom component constitution can help understand macroscopically observable optical properties.

Efficacy and Safety of Radiation Segmentectomy with 90Y Resin Microspheres for Hepatocellular Carcinoma.

Background Limited data are available on radiation segmentectomy (RS) for treatment of hepatocellular carcinoma (HCC) using yttrium 90 (90Y) resin microsphere doses determined by using a single-compartment medical internal radiation dosimetry (MIRD) model. Purpose To evaluate the efficacy and safety of RS treatment of HCC with 90Y resin microspheres using a single-compartment MIRD model and correlate posttreatment dose with outcomes. Materials and Methods This retrospective single-center study included adult patients with HCC who underwent RS with 90Y resin microspheres between July 2014 and December 2022. Posttreatment PET/CT and dosimetry were performed. Adverse events were assessed using the Common Terminology Criteria for Adverse Events, version 5.0. Per-lesion and overall response rates (ie, complete response [CR], objective response, disease control, and duration of response) were assessed at imaging using the Modified Response Evaluation Criteria in Solid Tumors, and overall survival (OS) was assessed using Kaplan-Meier analysis. Results Among 67 patients (median age, 69 years [IQR, 63-78 years]; 54 male patients) with HCC, median tumor absorbed dose was 232 Gy (IQR, 163-405 Gy). At 3 months, per-lesion and overall (per-patient) CR was achieved in 47 (70%) and 41 (61%) of 67 patients, respectively. At 6 months (n = 46), per-lesion rates of objective response and disease control were both 94%, and per-patient rates were both 78%. A total of 88% (95% CI: 79 99) and 72% (95% CI: 58, 90) of patients had a per-lesion and overall duration of response of 1 year or greater. At 1 month, a grade 3 clinical adverse event (abdominal pain) occurred in one of 67 (1.5%) patients. Median posttreatment OS was 26 months (95% CI: 20, not reached). Disease progression at 2 years was lower in the group that received 300 Gy or more than in the group that received less than 300 Gy (17% vs 61%; P = .047), with no local progression in the former group through the end of follow-up. Conclusion Among patients with HCC who underwent RS with 90Y resin microspheres, 88% and 72% achieved a per-lesion and overall duration of response of 1 year or greater, respectively, with one grade 3 adverse event. In patients whose tumors received 300 Gy or more according to posttreatment dosimetry, a disease progression benefit was noted. © RSNA, 2024 Supplemental material is available for this article.

Coastal and deep-sea biodegradation of polyhydroxyalkanoate microbeads.

Microbeads find widespread usage in personal care items and cosmetics, serving as exfoliants or scrubbing agents. Their micro-scale size poses challenges in effective drainage capture and given their origin from non-biodegradable oil-based plastics, this contributes substantially to marine pollution. In this study, microbeads were prepared by a simple yet scalable melt homogenization method using four types of polyhydroxyalkanoates (PHA), namely poly[(R)-3-hydroxybutyrate] (P(3HB)), poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyvalerate] (P(3HB-co-3HV)), poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate] (P(3HB-co-3HHx)) and poly[(R)-3-hydroxybutyrate-co-(R)-4-hydroxyvalerate] (P(3HB-co-4HB)). Microbeads with different surface smoothness, compressive strength (6.2-13.3 MPa) and diameter (from 1 ~ 150 µm) could be produced. The microbeads were subjected to a comprehensive degradation analysis using three techniques: enzymatic, Biochemical Oxygen Demand (BOD) evaluations, and in situ degradation tests in the deep-sea off Misaki Port in the northern Pacific Ocean (depth of 757 m). Qualitatively, results from enzymatic and in situ degradation demonstrated significant degradation within one week and five months, respectively. Quantitatively, BOD findings indicated that all PHA microbeads degraded similarly to cellulose (~ 85% biodegradability in 25 days). In conclusion, PHA microbeads from this study exhibit promising potential as alternatives to conventional non-biodegradable microbeads.

Synthesis and active manipulation of magnetic liquid beads.

We report the fabrication and characterisation of magnetic liquid beads with a solid magnetic shell and liquid core using microfluidic techniques. The liquid beads consist of a fluorinated oil core and a polymer shell with magnetite particles. The beads are generated in a flow-focusing polydimethylsiloxane (PDMS) device and cured by photo polymerisation. We investigated the response of the liquid beads to an external magnetic field by characterising their motion towards a permanent magnet. Magnetic sorting of liquid beads in a channel was achieved with 90% efficiency. The results show that the liquid beads can be controlled magnetically and have potential applications in digital microfluidics including nucleic acid amplification, drug delivery, cell culture, sensing, and tissue engineering. The present paper also discusses the magnetophoretic behaviour of the liquid bead by varying its mass and magnetite concentration in the shell. We also demonstrated the two-dimensional self-assembly of magnetic liquid beads for potential use in digital polymerase chain reaction and digital loop mediated isothermal amplification.

A Magnetic Pincher for the Dynamic Measurement of the Actin Cortex Thickness in Live Cells.

The actin cortex is an essential element of the cytoskeleton allowing cells to control and modify their shape. It is involved in cell division and migration. However, probing precisely the physical properties of the actin cortex has proved to be challenging: it is a thin and dynamic material, and its location in the cell-directly under the plasma membrane-makes it difficult to study with standard light microscopy and cell mechanics techniques. In this chapter, we present a novel protocol to probe dynamically the thickness of the cortex and its fluctuations using superparamagnetic microbeads in a uniform magnetic field. A bead ingested by the cell and another outside the cell attract each other due to dipolar forces. By tracking their position with nanometer precision, one can measure the thickness of the cortex pinched between two beads and monitor its evolution in time. We first present the set of elements necessary to realize this protocol: a magnetic field generator adapted to a specific imaging setup and the aforementioned superparamagnetic microbeads. Then we detail the different steps of a protocol that can be used on diverse cell types, adherent or not.

Release mechanism and pharmacodynamics of entecavir micro spheres.

Entecavir, an effective anti-hepatitis B drug with low resistance rate, was designed as sustained-release micro spheres in our previous study. Here, we aimed to reveal the drug-release mechanism by observing the drug distribution and degradation behavior of poly (lactic-co-glycolic acid) and to investigate the pharmacodynamics of entecavir micro spheres. Raman spectroscopy was used to analyze the distribution of active pharmaceutical ingredients in the micro spheres. The results showed that there was little entecavir near the micro sphere surface. With increasing micro sphere depth, the drug distribution gradually increased and larger-size entecavir crystals were mainly distributed near the spherical center. The degradation behavior of poly (lactic-co-glycolic acid) was investigated using gel permeation chromatography. Changes in poly (lactic-co-glycolic acid) molecular weights during micro sphere degradation revealed that dissolution dominated the release process, which proved our previous research results. Pharmacodynamics studies on transgenic mice indicated that the anti-hepatitis B virus replication effect was maintained for 42 days after a single injection of entecavir micro spheres, similar to the effect of daily oral administration of entecavir tablets for 28 days. The entecavir micro spheres prepared in this study had a good anti-hepatitis B virus replication effect and it is expected to be used in anti hepatitis B virus treatment against hepatitis B virus.

Synthesis of weak cation exchange/C18 bifunctional magnetic polymers for pretreatment and determination of glufosinate and its two metabolites in plasma samples.

This study focuses on the purification and detection of glufosinate (GLUF) and its metabolites N-acetyl GLUF and MPP in plasma samples. A Dikma Polyamino HILIC column was used for the effective retention and separation of GLUF and its metabolites, and the innovative addition of a low concentration of ammonium fluoride solution to the mobile phase effectively improved the detection sensitivity of the target analytes. Monodisperse core-shell weak cation exchange (WCX)/C18 bifunctional magnetic polymer composites (Fe3O4@WCX/C18) were prepared in a controllable manner, and their morphology and composition were fully characterized. The Fe3O4@WCX/C18 microspheres were used as a magnetic solid-phase extraction (MSPE) adsorbent for the sample purification and detection of GLUF and its metabolites in plasma samples combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The purification conditions of Fe3O4@WCX/C18 microspheres for GLUF and its metabolites in spiked plasma samples were optimized to achieve the best MSPE efficiency. The purification mechanisms of the target analytes in plasma samples include electrostatic attraction and hydrophobic interactions. Furthermore, the effect of the molar ratio of the two functional monomers 4-VBA and 1-octadecene in the adsorbent was optimized and it shows that the bifunctional components WCX/C18 have a synergistic effect on the determination of GLUF and its metabolites in plasma samples. In addition, the present study compared the purification performance of the Fe3O4@WCX/C18 microsphere-based MSPE method with that of the commercial Oasis WCX SPE method, and the results showed that the Fe3O4@WCX/C18 microsphere-based MSPE method established in this work had a stronger ability to remove matrix interferences. Under optimal purification conditions, the recoveries of GLUF and its metabolites in plasma were 87.6-111 % with relative standard deviations (RSDs) ranging from 0.2 % to 4.8 %. The limits of detection (LODs, S/N≥3) and limits of quantification (LOQs, S/N≥10) were 0.10-0.18 µg/L and 0.30-0.54 µg/L, respectively. The MSPE-LC-MS/MS method developed in this study is fast, simple, accurate and sensitive and can be used to confirm GLUF intoxication based not only on the detection of the GLUF prototype but also on the detection of its two metabolites.

Computational design and preparation of water-compatible noncovalent imprinted microspheres.

Herein, 2,4-dichlorophenoxyacetic acid (2,4-D) was used as a model template in a rational design strategy to produce water-compatible noncovalent imprinted microspheres. The proposed approach involved computational modelling for screening functional monomers and a simple method for preparing monodisperse and highly cross-linked microspheres. The fabricated non-imprinted polymer (NIP) and 2,4-d-imprinted polymer (2,4-d-MIP) were characterised, and their adsorption capabilities in an aqueous environment were evaluated. Results reveal that the pseudo-second-order kinetics model was appropriate for representing the adsorption of 2,4-D on NIP and 2,4-d-MIP, with R2 values of 0.97 and 0.99, respectively. The amount of 2,4-D adsorbed on 2,4-d-MIP (97.75 mg g-1) was considerably higher than those of phenoxyacetic acid (35.77 mg g-1), chlorogenic acid (9.72 mg g-1), spiramycin (1.56 mg g-1) and tylosin (1.67 mg g-1). Furthermore, it exhibited strong resistance to protein adsorption in an aqueous medium. These findings confirmed the feasibility of the proposed approach, providing a reference for the development of water-compatible noncovalent imprinted polymers.

LL37 Microspheres Loaded on Activated Carbon-chitosan Hydrogel: Anti-bacterial and Anti-toxin Wound Dressing for Chronic Wound Infections.

Antimicrobial peptide LL37 is a promising antibacterial candidate due to its potent antimicrobial activity with no known bacterial resistance. However, intrinsically LL37 is susceptible to degradation in wound fluids limits its effectiveness. Bacterial toxins which are released after cell lysis are found to hinder wound healing. To address these challenges, encapsulating LL37 in microspheres (MS) and loading the MS onto activated carbon (AC)-chitosan (CS) hydrogel. This advanced wound dressing not only protects LL37 from degradation but also targets bacterial toxins, aiding in the healing of chronic wound infections. First, LL37 MS and LL37-AC-CS hydrogel were prepared and characterised in terms of physicochemical properties, drug release, and peptide-polymer compatibility. Antibacterial and antibiofilm activity, bacterial toxin elimination, cell migration, and cell cytotoxicity activities were investigated. LL37-AC-CS hydrogel was effective against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. LL37-AC-CS hydrogel bound more endotoxin than AC with CS hydrogel alone. The hydrogel also induced cell migration after 72 h and showed no cytotoxicity towards NHDF after 72 h of treatment. In conclusion, the LL37-AC-CS hydrogel was shown to be a stable, non-toxic advanced wound dressing method with enhanced antimicrobial and antitoxin activity, and it can potentially be applied to chronic wound infections to accelerate wound healing.

Nanocomposite microbeads made of recycled polylactic acid for the magnetic solid phase extraction of xenobiotics from human urine.

Nanocomposite microbeads (average diameter = 10-100 µm) were prepared by a microemulsion-solidification method and applied to the magnetic solid-phase extraction (m-SPE) of fourteen analytes, among pesticides, drugs, and hormones, from human urine samples. The microbeads, perfectly spherical in shape to maximize the surface contact with the analytes, were composed of magnetic nanoparticles dispersed in a polylactic acid (PLA) solid bulk, decorated with multi-walled carbon nanotubes (mPLA@MWCNTs). In particular, PLA was recovered from filters of smoked electronic cigarettes after an adequate cleaning protocol. A complete morphological characterization of the microbeads was performed via Fourier-transform infrared (FTIR) spectroscopy, UV-Vis spectroscopy, thermogravimetric and differential scanning calorimetry analysis (TGA and DSC), scanning electron microscopy (SEM) and X-ray diffraction analysis (XRD). The recovery study of the m-SPE procedure showed yields ≥ 64%, with the exception of 4-chloro-2-methylphenol (57%) at the lowest spike level (3 µg L-1). The method was validated according to the main FDA guidelines for the validation of bioanalytical methods. Using liquid chromatography-tandem mass spectrometry, precision and accuracy were below 11% and 15%, respectively, and detection limits of 0.1-1.8 µg L-1. Linearity was studied in the range of interest 1-15 µg L-1 with determination coefficients greater than 0.99. In light of the obtained results, the nanocomposite microbeads have proved to be a valid and sustainable alternative to traditional sorbents, offering good analytical standards and being synthetized from recycled plastic material. One of the main objectives of the current work is to provide an innovative and optimized procedure for the recycling of a plastic waste, to obtain a regular and reliable microstructure, whose application is here presented in the field of analytical chemistry. The simplicity and greenness of the method endows the procedure with a versatile applicability in different research and industrial fields.

Injectable Modified Sodium Alginate Microspheres for Enhanced Operative Efficiency and Safety in Endoscopic Submucosal Dissection.

Endoscopic submucosal dissection (ESD) is an effective method for resecting early-stage tumors in the digestive system. To achieve a low injection pressure of the injected fluid and continuous elevation of the mucosa following injection during the ESD technique, we introduced an innovative injectable sodium-alginate-based drug-loaded microsphere (Cipro-ThSA) for ESD surgery, which was generated through an emulsion reaction involving cysteine-modified sodium alginate (ThSA) and ciprofloxacin. Cipro-ThSA microspheres exhibited notable adhesiveness, antioxidant activity, and antimicrobial properties, providing a certain level of postoperative wound protection. In vitro cell assays confirmed the decent biocompatibility of the material. Lastly, according to animal experiments involving submucosal elevation of porcine colons, Cipro-ThSA microspheres ensure surgically removable lift height while maintaining the mucosa for approximately 246% longer than saline, which could effectively reduce surgical risks while providing sufficient time for operation. Consequently, the Cipro-ThSA microsphere holds great promise as a novel submucosal injection material, in terms of enhancing the operational safety and effectiveness of ESD surgery.

Simultaneous Rosiglitazone Release and Low-Density Lipoprotein Removal by Chondroitin Sodium Sulfate/Cyclodextrin/Poly(acrylic acid) Composite Adsorbents for Atherosclerosis Therapy.

Atherosclerosis (AS) is characterized by the accumulation of substantial low-density lipoprotein (LDL) and inflammatory response. Hemoperfusion is commonly employed for the selective removal of LDL from the body. However, conventional hemoperfusion merely focuses on LDL removal and does not address the symptom of plaque associated with AS. Based on the LDL binding properties of acrylated chondroitin sodium sulfate (CSA), acrylated beta-cyclodextrin (CD) and acrylic acid (AA), along with the anti-inflammatory property of rosiglitazone (R), the fabricated AA-CSA-CD-R microspheres could simultaneously release R and facilitate LDL removal for hemoperfusion. The AA and CSA offer electrostatic adsorption sites for LDL, while the CD provides hydrophobic adsorption sites for LDL and weak binding sites for R. According to the Sips model, the maximum static LDL adsorption capacity of AA-CSA-CD-R is determined to be 614.73 mg/g. In dynamic simulated perfusion experiments, AA-CSA-CD-R exhibits an initial cycle LDL adsorption capacity of 150.97 mg/g. The study suggests that the weakened inflammatory response favors plaque stabilization. The anti-inflammatory property of the microspheres is verified through an inflammation model, wherein the microsphere extracts are cocultured with mouse macrophages. Both qualitative analysis of iNOS\TNF-α and quantitative analysis of IL-6\TNF-α collectively demonstrate the remarkable anti-inflammatory effect of the microspheres. Therefore, the current study presents a novel blood purification treatment of eliminating pathogenic factors and introducing therapeutic factors to stabilize AS plaque.

Fibrillogenesis in collagen hydrogels accelerated by carboxylated microbeads.

Collagen type I is a material widely used for 3D cell culture and tissue engineering. Different architectures, such as gels, sponges, membranes, and nanofibers, can be fabricated with it. In collagen hydrogels, the formation of fibrils and fibers depends on various parameters, such as the source of collagen, pH, temperature, concentration, age, etc. In this work, we study the fibrillogenesis process in collagen type I hydrogels with different types of microbeads embedded, using optical techniques such as turbidity assay and confocal reflectance microscopy. We observe that microbeads embedded in the collagen matrix hydrogels modify the fibrillogenesis. Our results show that carboxylated fluorescent microbeads accelerate 3.6 times the gelation, while silica microbeads slow down the formation of collagen fibrils by a factor of 1.9, both compared to pure collagen hydrogels. Our observations suggest that carboxylate microbeads act as nucleation sites and the early collagen fibrils bind to the microbeads.

Sodium alginate/carboxycellulose/polydopamine composite microspheres for rapid hemostasis of deep irregular wounds.

Hemostasis of deep irregular wounds is a severe problem in clinical practice. The development of rapid-acting hemostatic agents for deep and irregular wound is urgently needed. Here, sodium alginate/carboxycellulose/polydopamine (SA/CNF/PDA) microspheres was prepared by reverse emulsification and crosslinking with Ca2+, and SA/CNF/PDA composite hemostatic microspheres with porous structure were obtained by freeze-drying. SA/CNF/PDA composite hemostatic microspheres exhibited excellent porosity and water absorption which could rapidly absorb blood on the wound surface. Moreover, SA/CNF/PDA composite microspheres demonstrated remarkable hemostatic capabilities both in vitro and in vivo. It exhibited strong hemostatic performance in models of mouse tail-break and liver damage. Especially in liver injury model, it was completely hemostatic in 95 s, and blood loss (19.3 mg). The hemostatic efficacy of the SA/CNF/PDA composite microspheres was amplified through the stimulation of both exogenous and endogenous coagulation pathways. Therefore, SA/CNF/PDA composite hemostatic microspheres are suitable for rapid hemostasis of deep irregular wounds which are potential rapid hemostatic material for surgical application.

Preparation and sustained release of diatomite incorporated and Eudragit L100 coated hydroxypropyl cellulose/chitosan aerogel microspheres.

The drug encapsulation efficiency, release rate and time, sustained release, and stimulus-response of carriers are very important for drug delivery. However, these always cannot obtained for the carrier with a single component. To improve the comprehensive performance of chitosan-based carriers for 5-Fu delivery, diatomite-incorporated hydroxypropyl cellulose/chitosan (DE/HPC/CS) composite aerogel microspheres were fabricated for the release of 5-fluorouracil (5-Fu), and the release performance was regulated with the content of diatomite, pH value, and external coating material. Firstly, the 5-Fu loaded DE/HPC/CS composite aerogel microspheres and Eudragit L100 coated microspheres were prepared with cross-linking followed by freeze-drying, and characterized by SEM, EDS, FTIR, XRD, DSC, TG, and swelling. The obtained aerogel microspheres have a diameter of about 0.5 mm, the weight percentage of F and Si elements on the surface are 0.55 % and 0.78 % respectively. The glass transition temperature increased from 179 °C to 181 °C and 185 °C with the incorporation of DE and coating of Eudragit, and the equilibrium swelling percentage of DE/HPC/CS (1.5:3:2) carriers are 101.52 %, 45.27 %, 67.32 % at pH 1.2, 5.0, 7.4, respectively. Then, the effect of DE content on the drug loading efficiency of DE/HPC/CS@5-Fu was investigated, with the increase of DE content, the highest encapsulation efficiency was 82.6 %. Finally, the release behavior of DE incorporated and Eudragit L100 Coated microspheres were investigated under different pH values, and evaluated with four kinetic models. The results revealed that the release rate of 5-Fu decreased with the increase of DE content, sustained release with extending time and pH-responsive were observed for the Eudragit-coated aerogel microspheres.

Highly water-resistant paper via infiltration with polymeric microspheres from nanocellulose-stabilized plant oil-derived monomer.

Sustainable strategies to improve the water resistance of cellulose paper are actively sought. In this work, polymeric microspheres (PMs), prepared through emulsion polymerization of cellulose nanofibers stabilized rubber seed oil-derived monomer, were investigated as coatings on corrugated medium paper (CMP). After infiltrating porous paper with PMs, the water-resistant corrugated papers (WRCPn) with enhanced mechanical properties were obtained. When 30 wt% PMs were introduced, WRCP30 turned out to be highly compacted with an increased water contact angle of 106.3° and a low water vapor transmission rate of 81 g/(m2 d) at 23 °C. Meanwhile, the tensile strength of WRCP30 increased to 22.2 MPa, a 4-fold increase from CMP. When tested in a well-hydrated state, 71% of its mechanical strength in the dry state was maintained. Even with a low content of 10 wt% PMs, WRCP10 also exhibited stable tensile strength and water wettability during the cyclic soaking-drying process. Thus, the plant oil based sustainable emulsion polymers provide a convenient route for enhancing the overall performance of cellulose paper.

Combination of Doxorubicin and Antiangiogenic Agents in Drug-Eluting Beads: In Vitro Loading and Release Dynamics in View of a Novel Therapeutic Approach for Hepatocellular Carcinoma.

PURPOSE: Antiangiogenic agents have been used for many years as a first-line systemic treatment for advanced HCC. Embolization with cytostatic drugs on the other hand is the first-line treatment for intermediate HCC. The two types of drugs have not been combined for intraarterial delivery yet. The loading and release dynamics and the in vitro effect of their combination are tested in this experimental study. MATERIALS AND METHODS: Drug-eluting beads were loaded with doxorubicin, sunitinib and sunitinib analogue piperazine (SAP) alone and with their combinations. Diameter change, loading, release, and effect in cellular proliferation were assessed. RESULTS: The average microsphere diameter after loading was 473.7 µm (µm) for Doxorubicin, 388.4 µm for Sunitinib, 515.5 µm for SAP, 414.8 µm for the combination Doxorubicin/Sunitinib and 468.8 µm for the combination Doxorubicin /SAP. Drug release in 0.9% NaCl was 10% for Doxorubicin, 49% for Sunitinib, 25% for SAP, 20%/18% for the combination Doxorubicin/Sunitinib, and 18%/23% for the combination Doxorubicin/SAP whereas in human plasma it was 56%, 27%, 13%, 76%/63% and 62%/15%, respectively. The mean concentration of Doxorubicin that led to inhibition of 50% of cellular proliferation in an HCC Huh7 cell line was 163.1 nM (nM), for Sunitinib 10.3 micromolar (µΜ), for SAP 16.7 µΜ, for Doxorubicin/Sunitinib 222.4 nM and for Doxorubicin/SAP 275 nM. CONCLUSIONS: Doxorubicin may be combined with antiangiogenic drugs with satisfactory in vitro loading and release outcomes and effect on cellular lines.

Interferometric modulation for generating extended light sheet: improving field of view.

Significance: Light-sheet fluorescence microscopy (LSFM) has emerged as a powerful and versatile imaging technique renowned for its remarkable features, including high-speed 3D tomography, minimal photobleaching, and low phototoxicity. The interference light-sheet fluorescence microscope, with its larger field of view (FOV) and more uniform axial resolution, possesses significant potential for a wide range of applications in biology and medicine. Aim: The aim of this study is to investigate the interference behavior among multiple light sheets (LSs) in LSFM and optimize the FOV and resolution of the light-sheet fluorescence microscope. Approach: We conducted a detailed investigation of the interference effects among LSs through theoretical derivation and numerical simulations, aiming to find optimal parameters. Subsequently, we constructed a customized system of multi-LSFM that incorporates both interference light sheets (ILS) and noninterference light-sheet configurations. We performed beam imaging and microsphere imaging tests to evaluate the FOV and axial resolution of these systems. Results: Using our custom-designed light-sheet fluorescence microscope, we captured the intensity distribution profiles of both interference and noninterference light sheets (NILS). Additionally, we conducted imaging tests on microspheres to assess their imaging outcomes. The ILS not only exhibits a larger FOV compared to the NILS but also demonstrates a more uniform axial resolution. Conclusions: By effectively modulating the interference among multiple LSs, it is possible to optimize the intensity distribution of the LSs, expand the FOV, and achieve a more uniform axial resolution.

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.