Search Results (166)

Background/Objective: Osimertinib (OSI) is a third-generation tyrosine kinase inhibitor approved for non-small cell lung cancer (NSCLC) therapy. OSI is administered orally; this route limits the amount of OSI reaching the tumor in the lungs and is associated with serious systemic toxicity. This study aimed to develop a dry powder inhalable formulation to provide tumor-targeted delivery and minimize systemic toxicity. To the best of our knowledge, this is the first study to prepare and evaluate a dry powder inhalation formulation of OSI. Methods: Chitosan-coated PLGA nanoparticles (PLGA-C NPs) encapsulating OSI were prepared using a single emulsion-solvent evaporation technique. PLGA-C NPs were assembled into respirable nanocomposite microparticles (NCMPs) via spray drying with L-leucine as a carrier. PLGA-C NPs were characterized for particle size, zeta-potential, encapsulation efficiency, and in vitro efficacy in A-549 cell line. NCMPs were evaluated for solid-state properties, aerosolization performance, stability and in vitro release. Results: PLGA-C NPs exhibited a particle size of 145.18 ± 3.0 nm, high encapsulation efficiency and a positive zeta potential. In vitro studies demonstrated a 3.6-fold reduction in IC50 compared to free OSI, superior antimigratory effects and enhanced cell cycle arrest. Solid-state characterization of NCMPs demonstrated drug encapsulation in the polymer without chemical interaction. NCMPs exhibited excellent aerosolization (mass median aerodynamic diameter of 1.09 ± 0.23 μm, fine particle fraction of 73.48 ± 8.6%) and sustained drug release (61.76 ± 3.9% at 24 h). Stability studies confirmed the physicochemical stability integrity. Conclusions: These findings suggest that this novel dry powder inhalable OSI formulation may improve therapeutic outcomes while reducing systemic toxicity. Full article

Most nanoparticles and microparticles used as carriers of bioactive compounds are spherical in shape. Such particles are the easiest to obtain, as many processes spontaneously minimize the surface energy of the objects produced. However, in recent years, scientists have turned their attention to non-spherical particles in the hope of obtaining particles that interact with their environment in a tailored manner. The production of such particles should be easy and reproducible. The best candidates are spheroids produced by various methods. The most often used is the linear transformation of spheres during processes that preserve constant particle volume. The typical process consists of stretching a polymer matrix filled with spherical particles. The article delivers a critical overview of methods, discussing their advantages and disadvantages. A list of presented methods also includes the preparation of spheroids by polymer solution emulsification-solvent evaporation, controlled dispersion polymerization, electrohydrodynamic jetting, adsorption of amphiphilic copolymers on solid particles, and copolymer self-organization processes, as well as microfluidic methods, deformation of spherical particles into spheroids by irradiation, and phase microseparation. A special section is devoted to the self-organization of the particles at the phase boundaries. Eventually, the preparation and selected properties of two-dimensional and three-dimensional assemblies of spheroidal particles, particularly the preparation of a quasi-nematic colloidal crystal, are discussed. Full article

Solid–liquid stirred tanks are widely used in multiphase processes, including bioreactors for mesenchymal stem cell (MSC) culture, yet simultaneous experimental data for both dispersed and carrier phases remain limited. Here, a refractive index-matched (RIM) suspension of PMMA microparticles ($d_p=168\mathrm{\mu m}$, ${\rho }_p/{\rho }_l\approx 0.96$) in an NH₄SCN solution is studied at an intermediate Reynolds number ($Re\approx 5000$), low Stokes number ($St=0.078$), and particle volume fractions $0.1\le {\alpha }_p\le 0.5$ v%. This system was previously established and studied for the effect of addition of particles on the carrier phase. In this work, a dual-camera PIV set-up provides simultaneous velocity fields of the liquid and particle phases in a stirred tank equipped with a three-blade down-pumping HTPGD impeller. The liquid mean flow and circulation loop remained essentially unchanged with particle loading, whereas particle mean velocities were lower than single-phase and liquid-phase values in the impeller discharge. Turbulence levels diverged between phases: liquid-phase turbulent kinetic energy (TKE) in the impeller region increased modestly with ${\alpha }_p$, while solid-phase TKE was attenuated. Slip velocity maps showed that particles lagged the fluid in the impeller jet and deviated faster from the wall in the upward flow, with slip magnitudes increasing with ${\alpha }_p$. An approximate axial force balance indicated that drag dominates over lift in the impeller and wall regions, while the balance is approximately satisfied in the tank bulk, providing an experimental benchmark for refining drag and lift models in this class of stirred tanks. Full article

This review systematically outlines recent advances in long-acting microneedle-based transdermal drug delivery systems. It begins by introducing the fundamental principles of microneedles (MNs) as a minimally invasive technology and categorizes them by delivery mechanism into solid, coated, dissolving, hollow, hydrogel-forming, and biodegradable types. The review then discusses the design strategies and material platforms engineered for sustained drug release. A key focus is on biodegradable synthetic polymers, such as polylactic acid (PLA), poly (lactic-co-glycolic acid) (PLGA), and polycaprolactone (PCL), and natural polymers like silk fibroin (SF) and chitosan (CS), which enable prolonged drug release through their tunable degradation rates. Furthermore, it describes the incorporation of advanced drug carriers, including liposomes and polymeric nanoparticles/microparticles, into MNs to further extend release duration and enhance drug-loading capacity. Finally, the major challenges for clinical translation are addressed, including ensuring batch-to-batch consistency in manufacturing, maintaining sterility, and the necessity for more comprehensive validation of long-term in vivo efficacy and safety. Full article

Mesenchymal stem cells are widely cultivated in stirred tank bioreactors. Due to their adhesion properties, they are attached to small spherical spheres called microcarriers. To understand the hydromechanical stresses encountered by the cells, it is essential to characterize the flow using the PIV technique. However, the usual solid–liquid system used in cell cultures has poor optical properties. Thus, shifting to one with better optical properties, while respecting the physical characteristics, is mandatory to achieve a relevant representation. PMMA microparticles suspended with 61 wt% ammonium thiocyanate solution NH₄SCN were found to be a robust candidate. The refractive index (RI) of both sides is of the order of 1.491 with a density ratio of ${\rho }_f/{\rho }_p\approx$ 0.96, and particle size averaged around 168 μm. Using the RIM-PIV (refractive index matched particle image velocimetry) technique for a 0.7 L volume stirred tank equipped with an HTPG down-pumping axial impeller and operating at full homogeneous speed $N=150$ rpm, mean and turbulence quantities of the liquid phase were measured as a function of PMMA particle volume fractions ${\alpha }_p$, which ranged from 0.5 to 3 v%. This corresponds to a particle number density of $n=12$ particles/mm³, which is considered original and challenging for the PIV technique. At 3 v%, the addition of particles dampened the turbulent kinetic energy (TKE) of the liquid phase locally by 20% near the impeller. This impact became trivial (<10%) at the local-average level. The structure and direction of the recirculation loop also shifted. Full article

The direct deposition of highly concentrated polyelectrolyte complexes based on poly(ethyleneimine) (PEI) and poly(sodium methacrylate) (PMANa) onto inorganic sand microparticles (F100 and F200) resulted in the formation of versatile core-shell composites with fast removal properties in dynamic conditions toward anionic charged pollutants. Herein, in situ-generated nonstoichiometric PEI/PMANa polyelectrolyte complexes were directly precipitated as a soft organic shell onto solid sand microparticles at a 5% mass ratio (organic/inorganic part = 5%, w/w%). The sorption of an anionic model pollutant (Indigo Carmine (IC)) onto the composite particles in dynamic conditions depended on the inorganic core size, the flow rate, the bed type (fixed or fluidized) and the initial dye concentration. The maximum sorption capacity, after 10 cycles of sorption/desorption of IC onto F100@P5% and F200@P5%, was between 16 and 18 mg IC/mL composite. The newly synthesized core-shell composites could immobilize IC at a high flow rate (8 mL/min), either from concentrated (C_IC = 60 mg/L) or very diluted (C_IC = 0.2 mg/L) IC aqueous solution, demonstrating that this type of material could be promising in water treatment or efficient in solid-phase extraction (concentration factor of 2000). Full article

Background: The release study is a standard tool for the development, evaluation, and control of dosage forms. In the case of traditional drug delivery systems, it is conducted in accordance with the established principles available in the European and American Pharmacopoeias or guidelines proposed by registration agencies. The problem is the study of modern carriers, not yet described in compendia, which require adjustments to traditionally used methods. Objectives: The present study focuses on developing an optimal method for testing the release of cyclosporine (Cs, 0.5–4%) incorporated in solid lipid microparticles (SLM) dispersions (10%) intended for administration in the form of eye drops. This is a multicompartment lipid carrier that provides prolonged release of the active substance. Methods: Three methods of testing the release were compared: the dialysis bag method, the horizontal cells technique, and a method without a membrane. Results: During the analyses, the proper membrane was selected and the effect of the lysozyme enzyme on the release profile was analyzed. The effect of the composition of the acceptor fluid on the obtained results was also assessed. In the model without a membrane, up to 60% of the Cs was released within 30 min due to the burst effect. In horizontal chambers, no formulation released more than 14% of the Cs over 96 h, while at the same time, 60–70% of the Cs was released from the dialysis bag. Conclusions: Based on the obtained results, the dialysis bag method was selected to study the release of Cs from SLM without the need to use multicomponent artificial tear fluid as an acceptor medium. Full article

Friction stir spot welding (FSSW) is a solid-state joining technique increasingly favored in industries requiring high-quality, defect-free welds in lightweight and durable structures, such as the automotive, aerospace, and marine industries. This review examines the current advancements in FSSW, focusing on the relationships between microstructure, properties, and performance under load. FSSW offers numerous benefits over traditional welding, particularly for joining both similar and dissimilar materials. Key process parameters, including tool design, rotational speed, axial force, and dwell time, are discussed for their impact on weld quality. Innovations in robotics are enhancing FSSW’s accuracy and efficiency, while numerical simulations aid in optimizing process parameters and predicting material behavior. The addition of nano/microparticles, such as carbon nanotubes and graphene, has further improved weld strength and thermal stability. This review identifies areas for future research, including refining robotic programming, using artificial intelligence for autonomous welding, and exploring nano/microparticle reinforcement in FSSW composites. FSSW continues to advance solid-state joining technologies, providing critical insights for optimizing weld quality in sheet material applications. Full article

Resorbable microparticles can be added to hydrogel-based biocompatible scaffolds to improve their mechanical characteristics and allow localised drug delivery, which will aid in tissue repair and regeneration. It is well-known that bioprinting is important for producing scaffolds personalised to patients by loading them with their own cells and printing them with specified shapes and dimensions. The question is how the addition of such particles affects the rheological responsiveness of the hydrogels (which is critical during the printing process) as well as mechanical parameters like the elastic modulus. This study tries to answer this question using a specific system: an alginate-gelatine hydrogel containing polyhydroxybutyrate-co-hydroxyvalerate (PHBV) microparticles. Scaffolds were made by bioprinting and moulding incorporating PHBV microspheres (7–12 μm in diameter) into alginate–gelatine inks (4.5 to 9.0% w/v). The microparticles (MP) were predominantly located within the polymeric matrix at concentrations up to 10 mg MP/mL ink. Higher particle concentrations disrupted their spatial distribution. Inks pre-crosslinked with 15 mM calcium and containingMPat concentrations ranging from 0 to 10 mg/mL demonstrated rheological characteristics appropriate for bioprinting, such as solid-like behaviour (G′ = 1060–1300 Pa, G″ = 720–930 Pa), yield stresses of 320–400 Pa, and pseudoplastic behaviour (static viscosities of 4000–5600 Pa·s and ~100 Pa·s at bioprinting shear rates). Furthermore, these inks allow high printing quality, assessed through scaffold dimensions, filament widths, and printability (Pr > 0.94). The modulus of elasticity in compression (E) of the scaffolds varied according to the content of MP and the manufacturing technique, with values resembling those of soft tissues (200–600 kPa) and exhibiting a maximum reinforcement effect with 3 mg MP/mL ink (bioprinted E = 273 ± 28 kPa; moulded E = 541 ± 66 kPa). Over the course of six days, the sample’s mass and shape remained stable during degradation in simulated body fluid (SBF). Thus, the alginate–gelatine hydrogel loaded with PHBV microspheres inks shows promise for targeted drug delivery in soft tissue bioengineering applications. Full article

Active packaging using an edible coating could be an essential and sustainable alternative solution to preserve the properties of fruits and to prevent food loss and food waste. Fruits generate significant food wastes and losses. Reducing food waste is a global priority. For this research, nature-based solutions (NBSs) were applied, using micro-sized chitosan (CsMPs) and selenium microparticles (SeMPs), which are green-synthesized from black tea leaf extracts, and thyme essential oil. In this study, the effects of the new generation active food preservative coating agents formed from combinations of micro-sized chitosan (CsMPs) and selenium (SeMPs), and thyme essential oil (Oil) on the quality of “0900 Ziraat” sweet cherry fruits after harvest were investigated. After the fruits were coated with edible colloid solution, they were stored at 4 °C and 21 °C for 20 days, and quality parameter analyses were performed on days 0, 5, 10, 15, and 20. As a result of this study, it was determined that the application of CsMPs + SeMPs and the subsequent application of CsMPs + SeMPs + Oil from colloid solution coatings reduced weight loss, respiration, and decay rates. Also, it was determined that these applications were the most effective in preserving color values (L*, chroma, and hue), fruit firmness, total soluble solid (TSS) amount, acidity content and total phenolics, anthocyanin, and antioxidant capacity. These results show that CsMPs + SeMPs and CsMPs + SeMPs + Oil applications can be used as edible coatings to preserve the quality of sweet cherry fruits and extend their shelf life after harvest. This study’s results will contribute to obtaining micro-sized composite coating agents/agents produced with new technology to extend the shelf life. Full article

Solid lipid microparticles (SLMs) are multi-compartment lipid drug carriers that can be used in various forms via many routes of administration, primarily to obtain prolonged release, protect the drug substance or mask its taste. It is practically impossible to theoretically predict the effectiveness of the incorporation and distribution of active pharmaceutical ingredients (APIs) in SLMs, and these are fundamental features that determine the key properties of the dosage form. The possibility of an effective assessment of these features by selecting or developing sensitive, universal methods, therefore, conditions further development and practical use of this carrier. Therefore, unlike the already available review papers on SLMs, the aim of this mini-review is to focus solely on the issues of API distribution in SLMs and their release. For this purpose, the most important observations and results of our own research were collected and summarized, and then an attempt was made to confront them with the available literature data. Among the methods describing the critical attributes of SLMs, instrumental methods (DSC, AFM, Raman spectroscopy and NMR), quantitative studies for assessing API distribution in SLMs (including entrapment efficiency and drug-loading parameters) as well as different release techniques (without a membrane, in a dialysis bag and in horizontal chambers, taking into account physiological factors) were characterized and compared. The aim of this review is to facilitate the understanding of the SLM properties and to assess their ability to achieve the intended effect in vivo, as well as to standardize studies of such carriers, facilitating a comparison of the results between centers. Full article

Background: A hallmark of cancer is the presence of an immunosuppressive tumor microenvironment (TME). Immunosuppressive M2 macrophages (MΦs) in the TME facilitate escape from immune surveillance and promote tumor growth; therefore, TME-induced immunosuppression is a potent immunotherapeutic approach to treating cancer. Methods: Cancer cell-secreted proteins were detected by using liquid chromatography–mass spectrometry (LC-MS). Neutralizing antibodies (nAbs) were used to assess which proteins were involved in MΦs polarization and differentiation. The protein–protein interaction was characterized using co-immunoprecipitation and immunofluorescence assays. Cancer-secreted heat shock protein 70 (Hsp70) protein was quantified using an enzyme-linked immunosorbent assay (ELISA). MΦ polarization and tumor growth were assessed in vivo with subcutaneous LLC-GFP tumor models and toll-like receptor 2 (TLR2) knockout mice; in vitro assessments were conducted using TLR2 knockout and both LLC-GFP and LN227 lentiviral-mediated knockdown (KD) cells. Results: Cancer cells released a secreted form of Hsp70 that acted on MΦ TLR2 to upregulate Mer receptor tyrosine kinase (MerTK) and induce MΦ M2 polarization. Hsp70 nAbs led to a reduction in CD14 expression by 75% in THP-1 cells in response to Gli36 EMD-CM. In addition, neutralizing TLR2 nAbs resulted in a 30% and 50% reduction in CD14 expression on THP-1 cells in response to MiaPaCa-2 and Gli36 exosome/microparticle-depleted conditioned media (EMD-CMs), respectively. Hsp70, TLR2, and MerTK formed a protein complex. Tumor growth and intra-tumor M2 MΦs were significantly reduced upon cancer cell Hsp70 knockdown and in TLR2 knockout mice. Conclusions: Cancer-secreted Hsp70 interacts with TLR2, upregulates MerTK on MΦs, and induces immunosuppressive MΦ M2 polarization. This previously unreported action of secreted Hsp70 suggests that disrupting the Hsp70-TLR2-MerTK interaction could serve as a promising immunotherapeutic approach to mitigate TME immunosuppression in solid cancers. Full article

Background/Objectives: This study aimed to develop gastroretentive tablets based on mucoadhesive–floating systems with encapsulated gentian (Gentiana lutea, Gentianaceae) root extract to overcome the low bioavailability and short elimination half-life of gentiopicroside, a dominant bioactive compound with systemic effect. The formulation also aimed to promote the local action of the extract in the stomach. Methods: Tablets were obtained by direct compression of sodium bicarbonate (7.5%) and solid lipid microparticles (92.5%), which were obtained with lyophilizing double emulsions. A quality by design (QbD) was employed to evaluate the impact of formulation factors and processing parameters on emulsion viscosity, powder characteristics (moisture content, encapsulation efficiency, flowability), and tablet characteristics (floating lag time, gentiopicroside release, and assessment of dispersibility during in vitro dissolution). Results: The trehalose content and high-shear-homogenization (HSH) time of primary emulsion were critical factors. Trehalose content positively influenced emulsion viscosity, moisture content, floating lag time, encapsulation efficiency, and the release rate of gentiopicroside. HSH time positively affected powder stability and negatively gentiopicroside release. The selected powder had a high gentiopicroside encapsulation efficiency (95.13%), optimal stability, and good flowability. The developed tablets exhibited adequate floating lag time (275 s), mucoadhesive properties, and gentiopicroside biphasic release (29.04% in 45 min; 67.95% in 6 h). Furthermore, the optimal tablet formulation remained stable for 18 months and was primarily digested by duodenal enzymes. Conclusions: Dual-mechanism gastroretentive tablets with encapsulated gentian root extract were successfully developed. The in vitro digestion study demonstrated that the optimal formulation effectively resisted gastric enzymes, ensuring the release of its contents in the small intestine, even in the case of premature gastric evacuation. Full article

Microplastics are plastic particles ranging in size from 1 μm to 5 mm, emitted at the source or resulting from the degradation of larger objects. Today, their global distribution is one of the major environmental problems recognized by the United Nations Sustainable Development Goals, polluting aquatic, terrestrial and atmospheric systems and requiring avant-garde solutions. Solid–liquid filtration is widely used in both industrial and biological systems, where some aquatic species are examined using very specialized filter-feeding apparatus, and when applied to industrial processes, microparticles can be separated from the water while minimizing maintenance costs, as they require less backwashing or additional energy consumption. The REMOURE project uses the Mediterranean species Mobula mobular (Bonnaterre, 1788) as a reference for the testing and optimization of low-cost microplastic filters applied to wastewater. For this purpose, a hydrodynamic test rig was designed and constructed by considering the hydraulic feeding conditions of the marine species, with a scale factor of 6. This paper presents the design conditions and the evaluation of the test results for the combination of three different variables: (1) flap disposition (two different models were considered); (2) inclination with respect to the flow direction; and (3) flow velocity. The models were printed in polyamide and videos were recorded to evaluate the behaviour of dye injection through the lobes. The videos were processed, and the results were statistically treated and used to calibrate a CFD model to optimize the filter design to be studied in a prototype wastewater treatment plant. Full article

Aquaponics is an innovative agricultural method combining aquaculture and hydroponics. However, this balance can lead to the gradual depletion of essential micronutrients, particularly iron. Over time, decreasing iron levels can negatively impact plant health and productivity, making the monitoring and management of iron in aquaponic systems vital. This study investigates the use of Fe-Alg-CaCO₃ microparticles (MPs) as foliar fertilizer on lettuce plants in an aquaponic system. The research investigated Lactuca sativa L. cv. Foglia di Quercia Verde plants as the experimental cultivar. Three iron concentrations (10, 50, and 250 ppm) were tested, with 15 plants per treatment group, plus a control group receiving only sterile double-distilled water. The Fe-Alg-CaCO₃ MPs and ultrapure water were applied directly to the leaves using a specialized nebulizer. Foliar nebulization was chosen for its precision and minimal resource use, aligning with the sustainability goals of aquaponic cultivation. The research evaluated rosette diameter, root length, fresh weight, soluble solids concentration, levels of photosynthetic pigments, and phenolic and flavonoid content. The 250 ppm treatment produced the most notable enhancements in both biomass yield and quality, highlighting the potential of precision fertilizers to boost sustainability and efficiency in aquaponic systems. In fact, the most significant increases involved biomass production, particularly in the edible portions, along with photosynthetic pigment levels. Additionally, the analysis of secondary metabolite content, such as phenols and flavonoids, revealed no reduction compared to the control group, meaning that the proposed fertilizer did not negatively impact the biosynthetic pathways of these bioactive compounds. This study opens new possibilities in aquaponics cultivation, highlighting the potential of precision fertilizers to enhance sustainability and productivity in soilless agriculture. Full article