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17 pages, 1880 KiB  
Article
Dual-Phase Ocular Insert with Bromfenac-Loaded PLGA MPs in a PVA Matrix for Sustained Postoperative Anti-Inflammatory Delivery
by Farhan Alshammari, Bushra Alshammari, Asma Khalaf Alshamari, Kaushik Sarkar and Raghu Raj Singh Thakur
Pharmaceutics 2025, 17(8), 1066; https://doi.org/10.3390/pharmaceutics17081066 (registering DOI) - 17 Aug 2025
Abstract
Background: Postoperative ocular inflammation is a frequent complication of eye surgeries commonly managed using corticosteroids or nonsteroidal anti-inflammatory drug (NSAIDs) eye drops. However, poor ocular bioavailability and patient non-adherence due to frequent dosing limit the therapeutic efficacy of conventional eye drops. This study [...] Read more.
Background: Postoperative ocular inflammation is a frequent complication of eye surgeries commonly managed using corticosteroids or nonsteroidal anti-inflammatory drug (NSAIDs) eye drops. However, poor ocular bioavailability and patient non-adherence due to frequent dosing limit the therapeutic efficacy of conventional eye drops. This study aimed to develop a sustained-release ocular insert containing bromfenac sodium (BS)-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) with an initial 3% (w/w) free BS fraction incorporated into a poly(vinyl alcohol) (PVA) matrix designed to achieve a dual-phase release profile for improved postoperative therapy. Methods: PLGA-based MPs were fabricated using a double emulsion solvent evaporation technique and incorporated into PVA films to produce ocular inserts with varying MP content. Formulations were characterized for morphology, particle size, zeta potential, drug loading, entrapment efficiency, mucoadhesion, drug distribution, and in vitro release. Data were analyzed by an ANOVA and t-tests with p < 0.05 as significance. Results: MPs were smooth, spherical, and well-dispersed in the PVA inserts. Particle sizes ranged from 3.7 to 5.6 µm, with drug loading 7–8% and entrapment efficiencies 47–52%. Multiphoton imaging confirmed uniform drug distribution. In vitro release showed a dual-phase profile with an initial burst followed by sustained release for up to 4 days, with only negligible further release through Day 6 in one formulation (M1-7525). Conclusions: The developed BS-loaded PLGA MP/PVA insert demonstrated a dual-phase release profile relevant to postoperative ocular inflammation. Its biodegradable, single-application design holds promise for enhancing compliance and therapeutic outcomes in ophthalmic care. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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22 pages, 2535 KiB  
Article
From Recycled Polyethylene Terephthalate Waste to High-Value Chemicals and Materials: A Zero-Waste Technology Approach
by Maciej Kapkowski, Sonia Kotowicz, Karina Kocot, Mateusz Korzec, Jerzy Kubacki, Maciej Zubko, Krzysztof Aniołek, Urszula Siudyga, Tomasz Siudyga and Jaroslaw Polanski
Energies 2025, 18(16), 4375; https://doi.org/10.3390/en18164375 (registering DOI) - 17 Aug 2025
Abstract
The presence of PET (polyethylene terephthalate) in the environment is a global problem due to soil and water microplastic contamination. There is a constant demand for new technologies that expand the possibilities of PET disposal or recycling while reducing energy consumption and anthropogenic [...] Read more.
The presence of PET (polyethylene terephthalate) in the environment is a global problem due to soil and water microplastic contamination. There is a constant demand for new technologies that expand the possibilities of PET disposal or recycling while reducing energy consumption and anthropogenic carbon footprint. In this study, we developed a comprehensive zero-waste management system for PET recycling (rPET) to cyclic ketals and terephthalic acid. The developed method is based on the hydrolysis of rPET flakes in an inert environment with the separation and purification of terephthalic acid and the dehydration of ethylene glycol. For the first time, we present the use of cheap and readily available Cr/SiO2 and Fe/SiO2 nanocatalysts for direct acetalization of ethylene glycol without organic co-solvents. The catalysts were characterized by EDXRF, XPS and TEM techniques. The 2,2-dimethyl-1,3-dioxolane (DMD), a product of ethylene glycol’s direct acetalization with acetone, was tested as a solvent for polymers with satisfactory results in the solubility of epoxy resins. The addition of unpurified terephthalic acid and residues constituting post-production waste to concrete allows for a reduction in the mass of concrete in the range of 11.3–23.4% and the material modified in this way allows for a reduction in concrete consumption. This rPET waste management methodology is consistent with the assumptions of the circular economy and allows for a significant reduction of anthropogenic CO2 emissions. Full article
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14 pages, 24230 KiB  
Article
Optimizing Interfacial Adhesion and Mechanical Performance of Multimaterial Joints Fabricated by Material Extrusion
by Jakub Zatloukal, Mathieu Viry, Aleš Mizera, Pavel Stoklásek, Lukáš Miškařík and Martin Bednařík
Materials 2025, 18(16), 3846; https://doi.org/10.3390/ma18163846 (registering DOI) - 16 Aug 2025
Abstract
Multimaterial 3D printing is transforming the landscape of additive manufacturing, enabling the production of advanced, functional parts with tailored properties for sectors like automotive, aerospace, and engineering. However, achieving strong interlayer adhesion between different polymers remains a significant challenge, limiting the mechanical reliability. [...] Read more.
Multimaterial 3D printing is transforming the landscape of additive manufacturing, enabling the production of advanced, functional parts with tailored properties for sectors like automotive, aerospace, and engineering. However, achieving strong interlayer adhesion between different polymers remains a significant challenge, limiting the mechanical reliability. This study investigates adhesion properties of widely used materials—polycarbonate (PC), acrylonitrile styrene acrylate (ASA), polylactic acid (PLA), and polyethylene terephthalate glycol (PETG)—and enhances mechanical performance of structural joints through optimized interlayer bonding techniques. Using the Material Extrusion (MEX) method, tensile testing was employed to evaluate the mechanical strength of joints by co-depositing and bonding material layers during the printing process. The results demonstrate that specific material combinations and joint design strategies, particularly increasing the interfacial contact area and applying interlayer bonding pressure, significantly enhance tensile strength. For instance, the strength of PC/PTEG composite joints increased from 15.2 MPa (standard joint) to 29.9 MPa (interlayer bonding strategy), nearly doubling the bond strength. These findings provide valuable insights into the behavior of multimaterial joints and propose practical approaches for improving the durability and functionality of 3D-printed structures. This research lays the groundwork for advancing multimaterial additive manufacturing, with implications for high-performance applications in engineering, aerospace, and beyond. Full article
(This article belongs to the Special Issue Processing and Mechanical Properties of Polymer Composites)
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14 pages, 1678 KiB  
Article
Encapsulation of Therapeutic, Low-Molecular-Weight Chemokines Using a Single Emulsion, Microfluidic, Continuous Manufacturing Process
by Julie A. Kobyra, Michael Pezzillo, Elizabeth R. Bentley, Stephen C. Balmert, Charles Sfeir and Steven R. Little
Pharmaceutics 2025, 17(8), 1056; https://doi.org/10.3390/pharmaceutics17081056 - 14 Aug 2025
Viewed by 169
Abstract
Background/Objectives: Controlled release systems, such as polymeric microparticles (MPs), have emerged as a promising solution to extend the bioavailability and reduce dosing frequency for biologic drugs; however, the formulation of these systems to encapsulate highly sensitive, hydrophilic biologic drugs within hydrophobic polymers remains [...] Read more.
Background/Objectives: Controlled release systems, such as polymeric microparticles (MPs), have emerged as a promising solution to extend the bioavailability and reduce dosing frequency for biologic drugs; however, the formulation of these systems to encapsulate highly sensitive, hydrophilic biologic drugs within hydrophobic polymers remains a nontrivial task. Although scalable manufacturing and FDA approval of single emulsion processes encapsulating small molecules has been achieved, scaling more complex double emulsion processes to encapsulate hydrophilic biologics remains more challenging. Methods: Here, we demonstrate that two hydrophilic, low-molecular-weight, recombinant chemokines, CCL22 and CCL2, can be encapsulated in poly(lactic-co-glycolic acid) (PLGA) MPs using a single emulsion method where the proteins are dissolved in an organic solvent during formulation. Results: As expected, we observed some differences in release kinetics from single emulsion MPs compared to double emulsion MPs, which traditionally have been used to encapsulate proteins. Single emulsion MPs exhibited a substantially reduced initial burst. Importantly, protein released from single emulsion CCL22-MPs also retained biological activity, as determined by a cell-based functional assay. Decreasing particle size or changing the polymer end group from PLGA-COOH to PLGA-OH increased the initial burst from single emulsion MPs, demonstrating tunability of release kinetics for protein-loaded, single emulsion MPs. Finally, to improve scalability and enable more precise control over MP formulations, the single emulsion process was adapted to a microfluidic, continuous manufacturing system, and the resulting MPs were evaluated similarly. Conclusions: Altogether, this study demonstrates the feasibility of using a single emulsion encapsulation method for at least some protein biologics. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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8 pages, 1057 KiB  
Communication
Evaluation of PLA and PETG as 3D-Printed Reference Materials for Compressive Strength Testing
by Bartosz Budziński and Karol Federowicz
Materials 2025, 18(16), 3794; https://doi.org/10.3390/ma18163794 - 13 Aug 2025
Viewed by 226
Abstract
This study explores the feasibility of using 3D printing technology to fabricate reference materials for validating compressive strength measurements in construction laboratories. Polylactic acid (PLA) and polyethylene terephthalate glycol-modified (PETG) were selected due to their widespread availability and use in fused deposition modeling [...] Read more.
This study explores the feasibility of using 3D printing technology to fabricate reference materials for validating compressive strength measurements in construction laboratories. Polylactic acid (PLA) and polyethylene terephthalate glycol-modified (PETG) were selected due to their widespread availability and use in fused deposition modeling (FDM). A series of cubic samples with varying infill levels and dimensions were printed and tested to evaluate the influence of infill density, temperature, and storage time on compressive strength. PLA samples exhibited higher compressive strength values (from 23.5 kN for 10% infill to 70.7 kN for 50% infill) and a steeper increase in strength with rising infill density compared to PETG (from 12.4 kN for 10% infill to 44.1 kN for 50% infill). However, PETG demonstrated superior stability over time, with significantly smaller increases in result variability after 31 days. The results confirm a strong linear correlation between infill level and compressive strength and indicate that even small fluctuations in ambient temperature can influence test outcomes. Despite PLA’s initial mechanical advantage, PETG’s aging resistance makes it a promising candidate for the development of durable and repeatable reference materials (increment of StD for PLA from 0.17 kN to 0.63 kN and 0.25 kN to 0.37 for PET-G). This research contributes to closing the gap in the availability of reliable mechanical reference materials for destructive testing, offering a novel application for 3D printing in quality control in civil engineering. Full article
(This article belongs to the Section Materials Simulation and Design)
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25 pages, 1264 KiB  
Review
Deep Eutectic Solvent Systems as Media for the Selective Extraction of Anti-Inflammatory Bioactive Agents
by Beatriz Giner, Estela Sangüesa, Estefania Zuriaga, Laura Culleré and Laura Lomba
Molecules 2025, 30(16), 3357; https://doi.org/10.3390/molecules30163357 - 12 Aug 2025
Viewed by 313
Abstract
Bioactive compounds (BCs) are naturally occurring molecules found in plants, fungi, and microorganisms that can provide health benefits beyond nutrition. However, in order to administer them, they must be extracted from these organisms. This study reviews the extraction of anti-inflammatory bioactive compounds using [...] Read more.
Bioactive compounds (BCs) are naturally occurring molecules found in plants, fungi, and microorganisms that can provide health benefits beyond nutrition. However, in order to administer them, they must be extracted from these organisms. This study reviews the extraction of anti-inflammatory bioactive compounds using deep eutectic systems (DESs). It was found that DES extraction media can be categorized as either choline chloride-based or natural product-based (e.g., proline, betaine, and lactic acid). Results indicate that extraction yields depended on many factors such as extraction method and DES composition, with values ranging from 0.02 to 200 mg/g. For example, curcumin extraction using ChCl–propylene glycol (1:2), for example, reached 23.1 mg/g, whereas rutin extraction using ChCl–levulinic acid (1:2) achieved 200 mg/g. Regarding this, most of the eutectic mixtures used are choline chloride (ChCl)-based combined with sugars, polyalcohols, organic acids, or even water. Nonpolar DESs combining betaine, L-proline, amino acids, sugars, and organic acids have also been used for the extraction of BCs with anti-inflammatory potential. Although the use of DES offers significant advantages for extraction processes, certain limitations still need to be overcome. This review highlights the comparative advantages of DESs in terms of extraction efficiency and environmental sustainability, offering practical insights for selecting optimal systems to extract anti-inflammatory bioactive compounds. Full article
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45 pages, 4647 KiB  
Systematic Review
A Systematic Review of Biopolymer Phase Change Materials for Thermal Energy Storage: Challenges, Opportunities, and Future Direction
by Nadia Parwaty Wijanarko, Sindu Daniarta and Piotr Kolasiński
Energies 2025, 18(16), 4262; https://doi.org/10.3390/en18164262 - 11 Aug 2025
Viewed by 420
Abstract
This article systematically reviews biopolymer phase change materials (PCMs) for TES applications. The review was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using databases from Scopus, Web of Science, and Google Scholar. The biopolymer PCMs are categorized [...] Read more.
This article systematically reviews biopolymer phase change materials (PCMs) for TES applications. The review was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using databases from Scopus, Web of Science, and Google Scholar. The biopolymer PCMs are categorized as natural, synthetic, and hybrid (a combination of natural and synthetic). A total of 82 articles were included in the analysis. Several thermal properties, mechanical properties, advancements, and challenges are discussed. This article aims to review biopolymer PCMs and identify research gaps for future development. Natural biopolymer PCMs include lipid, lignin, polysaccharides, proteins, etc. Synthetic biopolymer PCMs include supramolecular, polyethylene glycol, polyurethane, polyrotaxane, polylactic acid, etc. Hybrid biopolymer PCMs combine natural and synthetic polymers with conductive fillers, balancing high latent heat with improved thermal stability and durability, although issues, like leakage and low conductivity, persist. It is found that biopolymers can be used as the core and supporting matrix of PCMs. Several cases and configurations of core, supporting matrix, and fillers in the development of PCM from biopolymers are discussed. This article also demonstrates that several natural, synthetic, and hybrid biopolymer PCMs hold promise for demanding TES applications due to their tunable properties and reliability. Biopolymer PCMs offer a sustainable alternative to petroleum-derived substances by minimizing environmental harm, cutting carbon emissions, and promoting a circular economy. This review also highlights several challenges, such as feedstock selection, purification and encapsulation, system compatibility, and standardization, that future research might address to enable scalable, safe, and cost-effective biopolymer PCM solutions. Full article
(This article belongs to the Section D: Energy Storage and Application)
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23 pages, 4238 KiB  
Article
Tuning Nanofibrous Sensor Performance in Selective Detection of B-VOCs by MIP-NP Loading
by Antonella Macagnano, Fabricio Nicolas Molinari, Simone Serrecchia, Paolo Papa, Anna Rita Taddei and Fabrizio De Cesare
Nanomaterials 2025, 15(16), 1220; https://doi.org/10.3390/nano15161220 - 9 Aug 2025
Viewed by 300
Abstract
In this study, we investigate the effect of varying the loading of molecularly imprinted polymer nanoparticles (MIP-NPs) on the morphology and sensing performance of electrospun nanofibres for the selective detection of linalool, a representative plant-emitted monoterpene. The proposed strategy combines two synergistic technologies: [...] Read more.
In this study, we investigate the effect of varying the loading of molecularly imprinted polymer nanoparticles (MIP-NPs) on the morphology and sensing performance of electrospun nanofibres for the selective detection of linalool, a representative plant-emitted monoterpene. The proposed strategy combines two synergistic technologies: molecular imprinting, to introduce chemical selectivity, and electrospinning, to generate high-surface-area nanofibrous sensing layers with tuneable architecture. Linalool-imprinted MIP-NPs were synthesized via precipitation polymerization using methacrylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA), yielding spherical particles with an average diameter of ~135 nm. These were embedded at increasing concentrations into a polyvinylpyrrolidone (PVP) matrix containing multi-walled carbon nanotubes (MWCNTs) and processed into nanofibrous mats by electrospinning. Atomic force microscopy (AFM) revealed that MIP content modulates fibre roughness and network morphology. Electrical sensing tests performed under different relative humidity (RH) conditions showed that elevated humidity (up to 60% RH) improves response stability by enhancing ion-mediated charge transport. The formulation with the highest MIP-NP loading exhibited the best performance, with a detection limit of 8 ppb (±1) and 84% selectivity toward linalool over structurally related terpenes (α-pinene and R-(+)-limonene). These results demonstrate a versatile sensing approach in which performance can be precisely tuned by adjusting MIP content, enabling the development of humidity-tolerant, selective VOC sensors for environmental and plant-related applications. Full article
(This article belongs to the Section Nanoelectronics, Nanosensors and Devices)
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27 pages, 3312 KiB  
Review
Influence of Structure–Property Relationships of Polymeric Biomaterials for Engineering Multicellular Spheroids
by Sheetal Chowdhury and Amol V. Janorkar
Bioengineering 2025, 12(8), 857; https://doi.org/10.3390/bioengineering12080857 - 9 Aug 2025
Viewed by 356
Abstract
Two-dimensional cell culture systems lack the ability to replicate the complex, three-dimensional (3D) architecture and cellular microenvironments found in vivo. Multicellular spheroids (MCSs) present a promising alternative, with the ability to mimic native cell–cell and cell–matrix interactions and provide 3D architectures similar to [...] Read more.
Two-dimensional cell culture systems lack the ability to replicate the complex, three-dimensional (3D) architecture and cellular microenvironments found in vivo. Multicellular spheroids (MCSs) present a promising alternative, with the ability to mimic native cell–cell and cell–matrix interactions and provide 3D architectures similar to in vivo conditions. These factors are critical for various biomedical applications, including cancer research, tissue engineering, and drug discovery and development. Polymeric materials such as hydrogels, solid scaffolds, and ultra-low attachment surfaces serve as versatile platforms for 3D cell culture, offering tailored biochemical and mechanical cues to support cellular organization. This review article focuses on the structure–property relationships of polymeric biomaterials that influence MCS formation, growth, and functionality. Specifically, we highlight their physicochemical properties and their influence on spheroid formation using key natural polymers, including collagen, hyaluronic acid, chitosan, and synthetic polymers like poly(lactic-co-glycolic acid) and poly(N-isopropylacrylamide) as examples. Despite recent advances, several challenges persist, including spheroid loss during media changes, limited viability or function in long-term cultures, and difficulties in scaling for high-throughput applications. Importantly, the development of MCS platforms also supports the 3R principle (Replacement, Reduction, and Refinement) by offering ethical and physiologically relevant alternatives to animal testing. This review emphasizes the need for innovative biomaterials and methodologies to overcome these limitations, ultimately advancing the utility of MCSs in biomedical research. Full article
(This article belongs to the Special Issue 3D Cell Culture Systems: Current Technologies and Applications)
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15 pages, 2161 KiB  
Article
Preparation of PLLA and PLGA Copolymers with Poly(ethylene adipate) Through Reactive Melt Mixing: Structural Characterization, Thermal Properties, and Molecular Mobility Insights
by Evi Christodoulou, Christina Samiotaki, Alexandra Zamboulis, Rizos Evangelos Bikiaris, Panagiotis A. Klonos, Apostolos Kyritsis and Dimitrios N. Bikiaris
Macromol 2025, 5(3), 35; https://doi.org/10.3390/macromol5030035 - 7 Aug 2025
Viewed by 203
Abstract
In this study, a series of copolymers was synthesized using the promising biodegradable polymers Poly(L-lactic acid) (PLLA), Poly(lactic-co-glycolic acid) (PLGA), and Poly(ethylene adipate) (PEAd), known for their high potential. PEAd was synthesized through a two-step melt polycondensation process and then used to prepare [...] Read more.
In this study, a series of copolymers was synthesized using the promising biodegradable polymers Poly(L-lactic acid) (PLLA), Poly(lactic-co-glycolic acid) (PLGA), and Poly(ethylene adipate) (PEAd), known for their high potential. PEAd was synthesized through a two-step melt polycondensation process and then used to prepare copolymers with PLLA (PLLA-co-PEAd) and PLGA (PLGA-co-PEAd) at weight ratios of 90/10 and 75/25, respectively. The synthesized materials, along with the starting polymers, were extensively characterized for their structure, molecular weight, crystallinity, and thermal behavior. These novel systems exhibit single thermal transitions, e.g., glass transition. The incorporation of PEAd into the copolymers induced a plasticizing effect, evidenced by a consistent decrease in the glass transition temperature. Due to the latter effect in combination with the Mw drop, the facilitation of crystal nucleation was observed. Finally, the results by dielectric spectroscopy on the local and segmental molecular mobility provided additional proof for the homogeneity of the systems, as manifested, e.g., by the recording of single segmental relaxation processes. Overall, the findings indicate that the PLLA-co-PEAd and PLGA-co-PEAd copolymers hold significant potential, and the use of complementary experimental techniques offers valuable insights and indirect indications of their properties. Full article
(This article belongs to the Collection Advances in Biodegradable Polymers)
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23 pages, 6941 KiB  
Article
Isolation and Characterization of Lignin from Sapele (Entandrophragma cylindricum): Application in Flexible Polyurethane Foam Production
by Hubert Justin Nnanga Guissele, Arnaud Maxime Cheumani Yona, Armel Edwige Mewoli, Désiré Chimeni-Yomeni, Lucioni Fabien Tsague, Tatiane Marina Abo, Jean-Bosco Saha-Tchinda, Maurice Kor Ndikontar and Antonio Pizzi
Polymers 2025, 17(15), 2156; https://doi.org/10.3390/polym17152156 - 6 Aug 2025
Viewed by 376
Abstract
Lignin used in this work was isolated from sapele (Entandrophragma cylindricum) wood through a hybrid pulping process using soda/ethanol as pulping liquor and denoted soda-oxyethylated lignin (SOL). SOL was mixed with a polyethylene glycol (PEG)–glycerol mixture (80/20 v/v) [...] Read more.
Lignin used in this work was isolated from sapele (Entandrophragma cylindricum) wood through a hybrid pulping process using soda/ethanol as pulping liquor and denoted soda-oxyethylated lignin (SOL). SOL was mixed with a polyethylene glycol (PEG)–glycerol mixture (80/20 v/v) as liquefying solvent with 98% wt. sulfur acid as catalyst, and the mixture was taken to boil at 140 °C for 2, 2.5, and 3 h. Three bio-polyols LBP1, LBP2, and LBP3 were obtained, and each of them exhibited a high proportion of -OH groups. Lignin-based polyurethane foams (LBPUFs) were prepared using the bio-polyols obtained with a toluene diisocyanate (TDI) prepolymer by the one-shot method. Gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FTIR), and carbon-13 nuclear magnetic resonance spectroscopy (13C NMR) were used characterize lignin in order to determine viscosity, yield, and composition and to characterize their structure. The PEG-400–glycerol mixture was found to react with the lignin bio-polyols’ phenolic -OHs. The bio-polyols’ viscosity was found to increase as the liquefaction temperature increased, while simultaneously their molecular weights decreased. All the NCO groups were eliminated from the samples, which had high thermal stability as the liquefaction temperature increased, leading to a decrease in cell size, density, and crystallinity and an improvement in mechanical performance. Based on these properties, especially the presence of some aromatic rings in the bio-polyols, the foams produced can be useful in automotive applications and for floor carpets. Full article
(This article belongs to the Section Circular and Green Sustainable Polymer Science)
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16 pages, 1674 KiB  
Article
Enhanced Anticancer Activity of Atractylodin-Loaded Poly(lactic-co-glycolic Acid) Nanoparticles Against Cholangiocarcinoma
by Tullayakorn Plengsuriyakarn, Luxsana Panrit and Kesara Na-Bangchang
Polymers 2025, 17(15), 2151; https://doi.org/10.3390/polym17152151 - 6 Aug 2025
Viewed by 351
Abstract
Cholangiocarcinoma (CCA) is highly prevalent in the Greater Mekong sub-region, especially northeastern Thailand, where infection with the liver fluke Opisthorchis viverrini is a major etiological factor. Limited therapeutic options and the absence of reliable early diagnosis tools impede effective disease control. Atractylodes lancea [...] Read more.
Cholangiocarcinoma (CCA) is highly prevalent in the Greater Mekong sub-region, especially northeastern Thailand, where infection with the liver fluke Opisthorchis viverrini is a major etiological factor. Limited therapeutic options and the absence of reliable early diagnosis tools impede effective disease control. Atractylodes lancea (Thunb.) DC.—long used in Thai and East Asian medicine, contains atractylodin (ATD), a potent bioactive compound with anticancer potential. Here, we developed ATD-loaded poly(lactic co-glycolic acid) nanoparticles (ATD PLGA NPs) and evaluated their antitumor efficacy against CCA. The formulated nanoparticles had a mean diameter of 229.8 nm, an encapsulation efficiency of 83%, and exhibited biphasic, sustained release, reaching a cumulative release of 92% within seven days. In vitro, ATD-PLGA NPs selectively reduced the viability of CL-6 and HuCCT-1 CCA cell lines, with selectivity indices (SI) of 3.53 and 2.61, respectively, outperforming free ATD and 5-fluorouracil (5-FU). They suppressed CL-6 cell migration and invasion by up to 90% within 12 h and induced apoptosis in 83% of cells through caspase-3/7 activation. Micronucleus assays showed lower mutagenic potential than the positive control. In vivo, ATD-PLGA NPs dose-dependently inhibited tumor growth and prolonged survival in CCA-xenografted nude mice; the high-dose regimen matched or exceeded the efficacy of 5-FU. Gene expression analysis revealed significant downregulation of pro-tumorigenic factors (VEGF, MMP-9, TGF-β, TNF-α, COX-2, PGE2, and IL-6) and upregulation of the anti-inflammatory cytokine IL-10. Collectively, these results indicate that ATD-PLGA NPs are a promising nanotherapeutic platform for targeted CCA treatment, offering improved anticancer potency, selectivity, and safety compared to conventional therapies. Full article
(This article belongs to the Section Polymer Applications)
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25 pages, 4393 KiB  
Article
Development and Preclinical Evaluation of Fixed-Dose Capsules Containing Nicergoline, Piracetam, and Hawthorn Extract for Sensorineural Hearing Loss
by Lucia Maria Rus, Andrei Uncu, Sergiu Parii, Alina Uifălean, Simona Codruța Hegheș, Cristina Adela Iuga, Ioan Tomuță, Ecaterina Mazur, Diana Șepeli, Irina Kacso, Fliur Macaev, Vladimir Valica and Livia Uncu
Pharmaceutics 2025, 17(8), 1017; https://doi.org/10.3390/pharmaceutics17081017 - 5 Aug 2025
Viewed by 383
Abstract
Background: Fixed-dose combinations have advanced in many therapeutic areas, including otorhinolaryngology, where hearing disorders are increasingly prevalent. Objectives: The present study focuses on developing and evaluating a new capsule combining nicergoline (NIC), piracetam (PIR), and hawthorn extract (HE) for the management of sensorineural [...] Read more.
Background: Fixed-dose combinations have advanced in many therapeutic areas, including otorhinolaryngology, where hearing disorders are increasingly prevalent. Objectives: The present study focuses on developing and evaluating a new capsule combining nicergoline (NIC), piracetam (PIR), and hawthorn extract (HE) for the management of sensorineural hearing loss. Methods: The first phase methodology comprised preformulation studies (DSC, FTIR, and PXRD) to assess compatibility among active substances and excipients. Subsequently, four formulations were prepared and tested for flowability, dissolution behavior in acidic and neutral media, and stability under oxidative, thermal, and photolytic stress. Quantification of the active substances and flavonoids was performed using validated spectrophotometric and HPLC-UV methods. Results: Among the tested variants, the F1 formulation (4.5 mg NIC, 200 mg PIR, 50 mg HE, 2.5 mg magnesium stearate, 2.5 mg sodium starch glycolate, and 240.5 mg monohydrate lactose per capsule) displayed optimal technological properties, superior dissolution in acidic media, and was further selected for evaluation. The antioxidant activity of the formulation was confirmed through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, Trolox Equivalent Antioxidant Capacity (TEAC), and iron chelation tests, and was primarily attributed to the flavonoid content of the HE. Acute toxicity tests in mice and rats indicated a high safety margin (LD50 > 2500 mg/kg), while ototoxicity assessments showed no adverse effects on auditory function. Conclusions: The developed formulation displayed good stability, safety, and therapeutic potential, while the applied workflow could represent a model for the development of future fixed-dose combinations. Full article
(This article belongs to the Special Issue Natural Product Pharmaceuticals, 2nd Edition)
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9 pages, 497 KiB  
Article
Ultra-Weak Photon Emission from Crown Ethers Exposed to Fenton’s Reagent Fe2+-H2O2
by Michał Nowak, Krzysztof Sasak, Anna Wlodarczyk, Izabela Grabska-Kobylecka, Agata Sarniak and Dariusz Nowak
Molecules 2025, 30(15), 3282; https://doi.org/10.3390/molecules30153282 - 5 Aug 2025
Viewed by 255
Abstract
We hypothesized that compounds containing ether linkages within their backbone structures, when exposed to hydroxyl radicals (•OH), can generate ultra-weak photon emission (UPE) as a result of the formation of triplet excited carbonyl species (3R=O*). To evaluate this hypothesis, we investigated [...] Read more.
We hypothesized that compounds containing ether linkages within their backbone structures, when exposed to hydroxyl radicals (•OH), can generate ultra-weak photon emission (UPE) as a result of the formation of triplet excited carbonyl species (3R=O*). To evaluate this hypothesis, we investigated the UPE of four compounds, each at a final concentration of 185.2 µmol/L: EGTA (ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid), a potent chelator of divalent cations, and three crown ethers—12-crown-4, 15-crown-5, and 18-crown-6—containing two, four, five, and six ether bonds, respectively. •OH was generated using a modified Fenton reagent—92.6 µmol/L Fe2+ and 2.6 mmol/L H2O2. The highest UPE was recorded for the Fe2+–EGTA–H2O2 (2863 ± 158 RLU; relative light units), followed by 18-crown-6, 15-crown-5, and 12-crown-4 (1161 ± 78, 615± 86, and 579 ± 109 RLU, respectively; p < 0.05), corresponding to the number of ether groups present. Controls lacking either H2O2 or Fe2+ exhibited no significant light emission compared to the buffer medium. These findings support the hypothesis that ether bonds, when oxidatively attacked by •OH, undergo chemical transformations resulting in the formation of 3R=O* species, the decay of which is associated with UPE. In crown ethers exposed to Fe2+-H2O2, the intensity of UPE was correlated with the number of ether bonds in their structure. Full article
(This article belongs to the Special Issue Molecular Insights into Bioluminescence and Chemiluminescence)
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11 pages, 490 KiB  
Article
Early Effect of Supplementation with Essential Amino Acids on Cardiac Performance in Elderly Patients with Heart Failure and Sarcopenia
by Giuseppe Armentaro, Velia Cassano, Pasquale Loiacono, Carlo Fuoco, Giandomenico Severini, Carlo Alberto Pastura, Alberto Panza, Marilisa Panza, Elisa Mazza, Sofia Miceli, Arturo Pujia, Tiziana Montalcini and Angela Sciacqua
Int. J. Mol. Sci. 2025, 26(15), 7533; https://doi.org/10.3390/ijms26157533 - 4 Aug 2025
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Abstract
The aim of the present observational study was to evaluate the early effect of free-form essential amino acid (EAA) supplementation on cardiac and muscular performance in elderly patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF) and sarcopenia, as add-on to [...] Read more.
The aim of the present observational study was to evaluate the early effect of free-form essential amino acid (EAA) supplementation on cardiac and muscular performance in elderly patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF) and sarcopenia, as add-on to the optimized medical therapy (OMT) for HF. The present study included 60 elderly Caucasian patients suffering from HFrEF and sarcopenia. At the baseline and at follow-up, all patients underwent complete physical examination with the determination of the main anthropometric and hemodynamic parameters. After 6 months of supplementation with EAAs, we observed significant improvements in the parameters of sarcopenia. In addition, there was a significant improvement in glycol-metabolic parameters, and in inflammatory index as high sensitivity C-reactive protein (hs-CRP). In accordance with these results, significant decreases were observed in circulating levels of oxidative stress biomarkers Nox-2 (p < 0.001) and 8-Isoprostane (p < 0.001), and platelet aggregation biomarkers such as sP-Selectin (p < 0.001) and Gp-VI (p < 0.001). Of particular interest, after 6 months’ follow-up, there was a significant improvement in LVEF and global longitudinal strain (GLS). In conclusion, this study demonstrates that targeted nutritional intervention with EEAAs represents a viable therapeutic strategy for addressing the complex interplay between cardiac dysfunction and skeletal muscle wasting in elderly HF patients. Full article
(This article belongs to the Special Issue Molecular Pathology and Treatment of Heart Failure)
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