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18 pages, 14411 KB  
Article
Synthesis of SiO2/g-C3N4/Bi2SiO5@Bi2O3 Nanohybrid: A Bifunctional Catalyst for Hydrogen Generation and Antitumor Applications
by Mohamed N. Goda, Mohamed Khairy and Babiker Y. Abdulkhair
Inorganics 2026, 14(7), 171; https://doi.org/10.3390/inorganics14070171 (registering DOI) - 24 Jun 2026
Abstract
The fascinating features of nanomaterials have attracted immense interest across various fields, including nanoelectronics, magnetite-aided nanocatalysis, and nanomedicine. Herein, a 10% SiO2/g-C3N4/Bi2SiO5@Bi2O3 triple nanohybrid was formulated via a simple protocol [...] Read more.
The fascinating features of nanomaterials have attracted immense interest across various fields, including nanoelectronics, magnetite-aided nanocatalysis, and nanomedicine. Herein, a 10% SiO2/g-C3N4/Bi2SiO5@Bi2O3 triple nanohybrid was formulated via a simple protocol employing acacia powder as a capping/fuel agent. The XRD confirmed the presence of g-C3N4, Bi2SiO5, Bi2O3, and SiO5 phases, and the TEM image shows densely packed, almost spherical nanoparticles of an average size of 9.2 nm. There was activity of the SiO2/g-C3N4/Bi2SiO5@Bi2O3 in the field of hydrogen generation via NaBH4 hydrolysis, and antitumor antiproliferation activity against HepG-2 and MCF-7 cells. The graphitized Bi2O3/SiO2 exhibited HGRs of 303, 615, 785, and 1740 mL min−1 g−1 at 20, 30, 40, and 50 °C, respectively. Hydrolyzing NaBH4 doses of 0.3, 0.5, 0.7, and 1.0 at 40 °C resulted in a dramatic evolution at HGRs of 526, 785, 1786, and 4000 mL min−1 g−1, respectively. Furthermore, the g-C3N4/Bi2O3/SiO2 antiproliferative effect against HepG-2 and MCF-7 cells showed a positive impact at 3.9 and 7.9 µg/mL, with IC50 values of 82.4 and 59.6 µg/mL, respectively. Moreover, the maximum dose of 500 μg/mL of SiO2/g-C3N4/Bi2SiO5@Bi2O3 resulted in 93.8% inhibition of MCF-7 cells, whereas the same dose yielded 91.7% inhibition of HepG-2 cells. It is significant to note that, given the lower cost of SiO2/g-C3N4/Bi2SiO5@Bi2O3 relative to currently prescribed antitumor medications, these outcomes can be considered ideal for practical use as antitumor agents. Full article
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40 pages, 2131 KB  
Review
Gold Nanoparticles for Antiviral Applications: Design Principles, Surface Engineering, and Mechanistic Insights
by Kang Shu, Yating Lei, Linjie Li, Shike Wang, Ting Du and Ting Tong
Pharmaceutics 2026, 18(7), 769; https://doi.org/10.3390/pharmaceutics18070769 (registering DOI) - 24 Jun 2026
Abstract
Gold nanoparticles (AuNPs) have emerged as versatile antiviral nanoplatforms because their size, morphology, plasmonic properties, and surface chemistry can be precisely engineered. In this review, we summarize the core design principles of antiviral AuNPs from a structure–function–mechanism perspective. We first outline representative synthetic [...] Read more.
Gold nanoparticles (AuNPs) have emerged as versatile antiviral nanoplatforms because their size, morphology, plasmonic properties, and surface chemistry can be precisely engineered. In this review, we summarize the core design principles of antiviral AuNPs from a structure–function–mechanism perspective. We first outline representative synthetic and interface-programming routes for AuNP preparation, including citrate reduction, Brust–Schiffrin synthesis, seed-mediated growth, green synthesis, direct thiol-conjugation, and mixed-ligand shell strategies, emphasizing how these approaches define particle size, morphology, surface accessibility, interfacial composition, and downstream biofunctionalization potential. We then discuss major surface engineering strategies, including polyethylene glycol, nucleic acids, antibodies and nanobodies, peptides, glycans, antiviral drugs, and biomimetic coatings, with particular attention to how ligand density, orientation, flexibility, and interfacial stability determine biological performance. Next, we examine how functionalized AuNPs inhibit different stages of the viral life cycle, including viral attachment and entry, intracellular replication, assembly and egress, photothermal inactivation, and immune modulation or vaccine delivery. Finally, we highlight current challenges, including incomplete structure–activity relationships, dynamic nano–bio interactions under physiological conditions, limited standardization across studies, and translational barriers related to safety, reproducibility, and scale-up. This review provides a conceptual framework for the rational development of next-generation AuNP-based antiviral nanotherapeutics. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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16 pages, 1551 KB  
Article
Changes in Resting Energy Expenditure in Response to Different Dietary Patterns: A Randomized Clinical Trial Exploratory Sub-Analysis
by Irene García-Gómez, Ainoa Mallorquín Castillo, Cristina Navas-Moreno, José Ignacio Martínez-Montoro, María Molina-Vega, Ana María Gómez-Pérez, Juan Alcaide-Torres, Alba Subiri-Verdugo, María Luisa García-Martín, Isabel Moreno-Indias and Francisco J. Tinahones
Nutrients 2026, 18(13), 2053; https://doi.org/10.3390/nu18132053 (registering DOI) - 24 Jun 2026
Abstract
Background: Evidence comparing the effects of novel alternative dietary strategies on resting energy expenditure (REE) with a hypocaloric standard Mediterranean diet (MedDiet) with continuous caloric restriction remains limited. This study aimed to evaluate the effects of diets with varying ketogenic potentials—including a very-low-carbohydrate [...] Read more.
Background: Evidence comparing the effects of novel alternative dietary strategies on resting energy expenditure (REE) with a hypocaloric standard Mediterranean diet (MedDiet) with continuous caloric restriction remains limited. This study aimed to evaluate the effects of diets with varying ketogenic potentials—including a very-low-carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF)—on the REE of individuals with obesity compared to those of a standard MedDiet. Methods: This was a secondary post hoc sub-analysis of a three-month, parallel-arm, randomized clinical trial (RCT) including 160 adults with obesity (body mass index > 30 kg/m2). The participants were randomly assigned to one of five calorie-restricted dietary interventions: control (MedDiet), KD, early time-restricted eating (eTRE), late time-restricted eating (lTRE), or mADF. All interventions featured an individualized energy deficit of 600 kcal/day. In this sub-analysis, a total of 102 participants with valid baseline measures were included. The REE was assessed by indirect calorimetry, and longitudinal trajectories were evaluated using Linear Mixed Models (LMMs) in 98 participants to account for baseline variability and to maximize data retention. Results: The mean age of participants in this sub-analysis was 45.3 years (SD 10.8), and 73.1% were women. The longitudinal modeling confirmed no statistically significant differences in the adjusted REE trajectories among the five dietary groups over the 3-month intervention (Group × Time interaction, p = 0.506). Furthermore, the LMMs showed that total body weight (p < 0.001) and biological sex (p < 0.001) were the variables most strongly associated with REE within the model. No independent associations between circulating beta-hydroxybutyrate levels and REE trajectories were detected. Conclusions: Hypocaloric diets with varying macronutrient distributions and fasting windows did not show statistically significant differences in REE trajectories over the 3-month intervention. In this exploratory sub-analysis, the REE trajectories were more closely associated with individual biological characteristics, particularly body weight and sex, than with the specific dietary strategy employed. Given the modest sample size and exploratory nature of the study, these findings should be interpreted cautiously and require confirmation in larger, adequately powered prospective trials. Full article
(This article belongs to the Section Nutrition and Metabolism)
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35 pages, 4094 KB  
Review
Renaissance of Traditional Mineral Drugs in Cancer: Advanced Delivery Strategies and Bioengineering Approaches
by Aolin Chen, Ping Luo, Jing Cao, Taohong Su, Xinxin Ding, Xinzhi Guo, Wenhao Zhou, Yang Chen and Fang Wang
Pharmaceutics 2026, 18(7), 768; https://doi.org/10.3390/pharmaceutics18070768 (registering DOI) - 23 Jun 2026
Abstract
Traditional mineral drugs represent an underexploited reservoir of natural antitumor agents; however, their clinical translation has historically been hindered by poor bioavailability, non-specific biodistribution, and dose-limiting toxicity. This review comprehensively examines the pharmacological mechanisms and modern formulation strategies driving the renaissance of mineral-based [...] Read more.
Traditional mineral drugs represent an underexploited reservoir of natural antitumor agents; however, their clinical translation has historically been hindered by poor bioavailability, non-specific biodistribution, and dose-limiting toxicity. This review comprehensively examines the pharmacological mechanisms and modern formulation strategies driving the renaissance of mineral-based oncology therapeutics. We highlight how mineral drugs exert potent anticancer effects through interconnected pathways, including regulated cell death (e.g., apoptosis, ferroptosis), cell-cycle arrest, and immunomodulation. Crucially, we evaluate recent advances in drug delivery systems, such as liposomes, polymeric nanoparticles, inorganic frameworks, and stimuli-responsive (e.g., pH, redox, enzyme) release systems that successfully overcome traditional pharmacological barriers. These bioengineering strategies not only improve solubility and tumor targeting but also significantly widen the therapeutic window, as evidenced by enhanced tumor suppression and reduced systemic toxicity in preclinical models. Despite this progress, challenges regarding in vivo chemical transformations and tumor heterogeneity remain. Ultimately, we propose a closed-loop “Composition–Mechanism–Delivery” design paradigm to guide future research, facilitating the translation of ethnopharmacological heritage into precision mineral-based therapeutics. Full article
(This article belongs to the Special Issue Advanced Drug Delivery Systems for Natural Products)
33 pages, 2848 KB  
Article
Development and Optimization of 7,8-Dihydroxyflavone-Loaded Polylysine/Lecithin Nanoparticles for Potential Intranasal Delivery
by Sonya Salamone, Rosalia Pellitteri, Ilaria Ottonelli, Elide Zingale, Cinzia Cimino, Barbara Ruozi, Teresa Musumeci and Rosario Pignatello
Pharmaceutics 2026, 18(7), 766; https://doi.org/10.3390/pharmaceutics18070766 (registering DOI) - 23 Jun 2026
Abstract
Background: Effective strategies for delivering neuroprotective agents to the brain remain a major challenge due to the poor solubility, rapid metabolism, and low bioavailability of promising molecules, such as 7,8-dihydroxyflavone (7,8-DHF). This small-molecule TrkB receptor agonist exhibits significant antioxidant, neuroprotective properties, and [...] Read more.
Background: Effective strategies for delivering neuroprotective agents to the brain remain a major challenge due to the poor solubility, rapid metabolism, and low bioavailability of promising molecules, such as 7,8-dihydroxyflavone (7,8-DHF). This small-molecule TrkB receptor agonist exhibits significant antioxidant, neuroprotective properties, and additional effects on metabolic regulation, but its therapeutic potential is limited by unfavorable pharmacokinetic characteristics. Nanotechnology-based delivery systems are increasingly explored to improve drug stability, enhance bioavailability, and facilitate direct nose-to-brain transport following intranasal administration. In this study, lipid nanoparticles encapsulating 7,8-DHF were developed using a fish-oil-based lipid core enriched with ω-3 polyunsaturated fatty acids (DHA and EPA) and naturally derived excipients, including soybean lecithin and ε-polylysine. Methods: The formulation was optimized using a Design of Experiments (DoE) approach based on a 23 full factorial design, evaluating drug concentration, lecithin concentration, and surfactant type (Pluronic® F127 or Tween® 80). The main formulation responses considered were particle size, polydispersity index (PDI), zeta potential, and encapsulation efficiency. Results: The optimized nanoparticles exhibited nanometric dimensions (<250 nm); spherical morphology, confirmed by TEM; low polydispersity (PDI < 0.3); and adequate encapsulation efficiency. Stability studies in simulated biological fluids indicated good physicochemical stability for up to 48 h, while interaction studies with mucin suggested a good interaction within the mucus environment. ROS scavenging capacity was confirmed through the DPPH chemical assay, and in vitro experiments on olfactory ensheathing cells, selected as a biologically relevant model for their anatomical localization along the olfactory pathway, showed reduced cytotoxicity of the encapsulated drug compared with the free form. Conclusions: Collectively, these results support the potential application of the developed nanoformulation in the intranasal delivery of 7,8-DHF. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
47 pages, 2613 KB  
Review
Artificial Intelligence in Nanopharmaceutical Development: From Predictive Design to Clinical Translation
by Renato Sonchini Gonçalves
Pharmaceutics 2026, 18(6), 764; https://doi.org/10.3390/pharmaceutics18060764 (registering DOI) - 22 Jun 2026
Viewed by 176
Abstract
Artificial intelligence (AI) is increasingly influencing nanopharmaceutical development by supporting the transition from empirical formulation screening toward predictive, data-driven, and translationally oriented design. Nanocarrier-based therapeutics are governed by nonlinear relationships among material composition, physicochemical attributes, manufacturing parameters, biological identity, pharmacokinetics, toxicity, and therapeutic [...] Read more.
Artificial intelligence (AI) is increasingly influencing nanopharmaceutical development by supporting the transition from empirical formulation screening toward predictive, data-driven, and translationally oriented design. Nanocarrier-based therapeutics are governed by nonlinear relationships among material composition, physicochemical attributes, manufacturing parameters, biological identity, pharmacokinetics, toxicity, and therapeutic performance. In this review, we examine how AI can contribute to nanopharmaceutical development from predictive formulation design to clinical translation. We synthesize current applications of machine learning, deep learning, physics-informed modeling, hybrid mechanistic–AI approaches, and automated optimization workflows, with emphasis on critical quality attribute modeling, multi-objective optimization, design of experiments, quality-by-design, process analytical technology, digital twins, and continuous manufacturing. We also discuss applications involving nano–bio interactions, pharmacokinetics, toxicity, immunogenicity, and precision nanomedicine. AI-based approaches can support rational nanocarrier design, identify nonlinear formulation–property relationships, guide optimization, improve process understanding, and integrate heterogeneous experimental, biological, and manufacturing datasets across diverse nanopharmaceutical platforms. These methods are particularly relevant for modeling protein corona formation, cellular uptake, intracellular trafficking, biodistribution, pharmacokinetics, toxicity, immunogenicity, and patient-specific responses. However, translational implementation remains limited by fragmented datasets, inconsistent reporting standards, limited interpretability, insufficient external validation, uncertain predictions, poorly defined applicability domains, and evolving regulatory expectations for adaptive computational models. Overall, AI should be viewed not only as an optimization tool, but also as a translational framework connecting formulation science, biological prediction, manufacturing control, and clinical implementation. Future progress will depend on standardized data infrastructures, explainable and externally validated models, uncertainty quantification, applicability-domain definition, hybrid mechanistic–AI frameworks, regulatory-ready documentation, and clinically relevant case studies. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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20 pages, 1716 KB  
Review
Flavonoids in Cancer Therapy: Nanocarrier Strategies to Overcome Bioavailability Limitations
by Maykon Jhuly Martins de Paiva, Walmirton Bezerra D’Alessandro, Iangla Araújo de Melo Damasceno, Juliane Farinelli Panontin, Taides Tavares dos Santos, Sávia Denise Silva Carlotto Herrera, Mateus Silva Santos and Márcio Trevisan
Sci. Pharm. 2026, 94(2), 51; https://doi.org/10.3390/scipharm94020051 (registering DOI) - 19 Jun 2026
Viewed by 319
Abstract
Flavonoids are a structurally diverse class of plant-derived polyphenolic compounds widely recognized for their pleiotropic biological activities, including antioxidant, anti-inflammatory, and anticancer effects. In oncology, these compounds have demonstrated the ability to modulate key signaling pathways involved in cell proliferation, apoptosis, angiogenesis, and [...] Read more.
Flavonoids are a structurally diverse class of plant-derived polyphenolic compounds widely recognized for their pleiotropic biological activities, including antioxidant, anti-inflammatory, and anticancer effects. In oncology, these compounds have demonstrated the ability to modulate key signaling pathways involved in cell proliferation, apoptosis, angiogenesis, and metastasis, highlighting their potential as multitarget therapeutic agents. However, their clinical translation remains significantly limited by unfavorable pharmacokinetic properties, such as poor aqueous solubility, extensive first-pass metabolism, rapid systemic clearance, and consequently low oral bioavailability. In this context, nanotechnology has emerged as a promising strategy to overcome these limitations. This review provides a comprehensive and critical analysis of current nanocarrier-based delivery systems for flavonoids, including polymeric nanoparticles, lipid-based nanocarriers (liposomes, solid lipid nanoparticles, and nanoemulsions), micelles, and cyclodextrin complexes, emphasizing their role in improving drug stability, enhancing cellular uptake, and enabling targeted delivery to tumor tissues through both passive mechanisms, such as the enhanced permeability and retention effect, and active targeting approaches. In addition, recent in vitro and in vivo studies demonstrating the superior antitumor efficacy of nanoencapsulated flavonoids compared to free compounds are discussed. Finally, the major translational challenges, safety considerations, and future perspectives for the clinical application of flavonoid-based nanomedicines in cancer therapy are highlighted. Full article
(This article belongs to the Special Issue Anticancer Potential of Natural Products)
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36 pages, 3626 KB  
Review
Smart Nanomaterials and Natural Biologics for Innate–Adaptive Immune Reprogramming: A Nanobiotechnology Framework for Translational Medicine
by Kawther Zaher, Mai M. El-Daly, Sherif A. El-Kafrawy, Aymn T. Abbas, Umama A. Abdel-dayem and Zeenat Mirza
Nanomaterials 2026, 16(12), 770; https://doi.org/10.3390/nano16120770 (registering DOI) - 18 Jun 2026
Viewed by 255
Abstract
The innate–adaptive immune interface is a decisive control point determining whether therapeutic interventions induce durable protection, antitumor immunity, inflammatory, or immune tolerance. Many immunotherapies fail in translation because immunity is often treated as a single-output system rather than a spatially and temporally organized [...] Read more.
The innate–adaptive immune interface is a decisive control point determining whether therapeutic interventions induce durable protection, antitumor immunity, inflammatory, or immune tolerance. Many immunotherapies fail in translation because immunity is often treated as a single-output system rather than a spatially and temporally organized network shaped by tissue context, antigen-presenting cell fate, biomolecular conditioning, and metabolic state. This review introduces the immunoscape framework as a nanobiotechnology-oriented model for linking immune-state mapping with controllable translational variables, including delivery route, release kinetics, first-contact immune cells, lymphatic routing, biomolecular corona identity, antigen-presenting cell fate, and safety-gate assessment. Unlike systems immunology, which primarily describes immune networks, or conventional immune engineering, which often focuses on selected payloads, targets, or platforms, the immunoscape framework provides a design layer for predicting context-dependent immune outcomes. We discuss two converging strategies for reprogramming this interface: natural biologics, including beta-glucans, polyphenols, microbial metabolites, and extracellular vesicles; and smart nanomaterials, including lipid nanoparticles, biomimetic vesicles, lymph node-targeted platforms, and stimulus-responsive nanoarchitectures. We further propose translational design rules to guide clinically realistic immune-reprogramming nanomedicines for cancer, infectious, inflammatory, and regenerative applications. Full article
(This article belongs to the Special Issue Nanobiotechnology in Biology and Medicine)
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21 pages, 618 KB  
Review
Nanomedicine in Cardiovascular Inflammation: Novel Diagnostic and Therapeutic Strategies
by Aikaterini-Eleftheria Karanikola, Agapi Ploussi, Dimitrios Tsiachris and Efstathios P. Efstathopoulos
J. Pers. Med. 2026, 16(6), 328; https://doi.org/10.3390/jpm16060328 - 18 Jun 2026
Viewed by 253
Abstract
Inflammation plays a central role in the pathogenesis and progression of cardiovascular diseases, including atherosclerosis, myocardial infarction and heart failure. Despite advances in conventional diagnostic and therapeutic strategies, limitations in sensitivity, specificity and targeted drug delivery still remain. Nanomedicine has emerged as a [...] Read more.
Inflammation plays a central role in the pathogenesis and progression of cardiovascular diseases, including atherosclerosis, myocardial infarction and heart failure. Despite advances in conventional diagnostic and therapeutic strategies, limitations in sensitivity, specificity and targeted drug delivery still remain. Nanomedicine has emerged as a promising yet underexplored approach to address these challenges by enabling precise molecular imaging and site-specific therapeutic interventions. This review summarizes current and emerging nanotechnology-based approaches for the diagnosis and treatment of cardiovascular inflammation, highlighting their potential in clinical practice and remaining challenges. In addition, recent advances, including the development of biomimetic nanoplatforms, are discussed, along with future perspectives and the potential integration of artificial intelligence to further enhance precision in cardiovascular medicine. Full article
(This article belongs to the Special Issue Personalized Prevention and Treatment of Cardiovascular Diseases)
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42 pages, 3543 KB  
Review
Emerging Perspectives on How Metallic Nanoparticles and Their Oxide Forms Interact with the Tumor Microenvironment
by Carlos Caro
Processes 2026, 14(12), 1977; https://doi.org/10.3390/pr14121977 (registering DOI) - 18 Jun 2026
Viewed by 303
Abstract
Cancer remains one of the most formidable health challenges worldwide. Extensive research has shown that tumor progression is not driven solely by malignant cells but is profoundly shaped by the tumor microenvironment (TME), which influences cancer initiation, immune evasion, and metastatic spread. Consequently, [...] Read more.
Cancer remains one of the most formidable health challenges worldwide. Extensive research has shown that tumor progression is not driven solely by malignant cells but is profoundly shaped by the tumor microenvironment (TME), which influences cancer initiation, immune evasion, and metastatic spread. Consequently, the TME has become an increasingly compelling therapeutic target. Nanotechnology has transformed cancer diagnostics and therapy, with metallic nanoparticles (mNPs) gaining particular attention due to their distinctive physicochemical properties and broad therapeutic potential. However, their interactions within the TME remain insufficiently understood, particularly with the non-cancerous cellular components, such as Cancer-Associated Fibroblasts (CAFs), Tumor-Associated Macrophages (TAMs), Dendritic Cells (DCs), Natural Killer (NK) cells, and T cells. Most existing reviews emphasize nanoparticle interactions with non-cellular TME components, such as the extracellular matrix, while far less attention has been given to their effects on cellular constituents (a gap this work specifically addresses). Although several molecular pathways through which mNPs modulate TME-resident cells have been identified, these likely represent only a small portion of the underlying mechanisms explored in this review. Progress in the field is further hindered by the limited availability of physiologically relevant experimental models; current in vitro and in vivo systems often fail to capture the complexity and dynamic heterogeneity of the TME. These limitations highlight the urgent need for more comprehensive and mechanistically grounded studies to validate the TME as a viable therapeutic target for nanoparticle-based cancer interventions. In particular, deeper insights into how mNPs influence immune regulation, stromal remodeling, and metabolic reprogramming within the TME will be essential for unlocking their full therapeutic potential in oncology. Full article
(This article belongs to the Special Issue Multiscale Modeling and Control of Biomedical Systems)
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25 pages, 4365 KB  
Article
Effect of Black Rice Starch on Structure and Physical–Mechanical Properties of Carboxymethyl Chitosan/Gellan Gum-Based Intelligent Food Packaging Film and Application in Monitoring Shrimp Freshness
by Siti Ayu Ulfadillah, I-Lin Tsai, Chi Lin, Yu-Hao Huang, Yi-Cheng Ho, Min-Lang Tsai and Fwu-Long Mi
Polymers 2026, 18(12), 1505; https://doi.org/10.3390/polym18121505 - 16 Jun 2026
Viewed by 343
Abstract
Visual freshness monitoring is challenging in intelligent seafood packaging. This study developed low-acyl gellan gum (LGG)-based intelligent films incorporating anthocyanin (BRE), carboxymethyl chitosan (CMCh), and black rice starch (BRS) and evaluated their effects on film structure, physical–mechanical properties, and shrimp freshness-monitoring performance. Films [...] Read more.
Visual freshness monitoring is challenging in intelligent seafood packaging. This study developed low-acyl gellan gum (LGG)-based intelligent films incorporating anthocyanin (BRE), carboxymethyl chitosan (CMCh), and black rice starch (BRS) and evaluated their effects on film structure, physical–mechanical properties, and shrimp freshness-monitoring performance. Films prepared via solution casting were evaluated using structural, mechanical, and barrier analyses, alongside shrimp spoilage trials at 25 °C. Structural analyses revealed an integrated polysaccharide network. CMCh reinforced the matrix and increased tensile strength, whereas partially retained BRS granules introduced microstructural heterogeneity, reducing strength and increasing water vapor permeability, highlighting a trade-off between mechanical performance and moisture transport. Consequently, BRS-containing films reduced BRE release, improved pigment retention, and resulted in less intense color changes associated with total volatile basic nitrogen (TVB-N) accumulation during shrimp spoilage. Overall, these results suggest that CMCh and BRS composition-dependently modulate the structure, water vapor transport, pigment retention, and colorimetric response of LGG-based films for visual monitoring of shrimp freshness under accelerated spoilage conditions. Full article
(This article belongs to the Special Issue Polysaccharides in Food Applications)
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30 pages, 4306 KB  
Review
Physicochemical Aspects of Mixed Micelle Formation Between Amphiphilic Drugs and Surfactants
by Ádám Juhász, Bianka Torma, Egon F. Várkonyi, László Seres, Norbert Varga, Árpád Turcsányi and Edit Csapó
Int. J. Mol. Sci. 2026, 27(12), 5400; https://doi.org/10.3390/ijms27125400 - 15 Jun 2026
Viewed by 168
Abstract
The rational design of mixed micellar systems has emerged as a cornerstone of modern nanomedicine, offering unprecedented control over the solubility and bioavailability of challenging therapeutic agents. This review provides a comprehensive analysis of the physicochemical principles governing the assembly of amphiphilic drugs [...] Read more.
The rational design of mixed micellar systems has emerged as a cornerstone of modern nanomedicine, offering unprecedented control over the solubility and bioavailability of challenging therapeutic agents. This review provides a comprehensive analysis of the physicochemical principles governing the assembly of amphiphilic drugs and surfactants into synergistic nanostructures. By articulating the transition from traditional guest/host solubilization to “drug-as-component” models, we highlight the critical role of molecular interactions in achieving therapeutic precision. It further outlines the experimental methodologies used to investigate these systems and elucidates how they enhance the solubility, stability, and bioavailability of poorly water-soluble drugs. Special emphasis is placed on the practical applications of synergy in reducing systemic toxicity and optimizing drug release kinetics, providing a roadmap for the development of next-generation nano-pharmaceuticals. The functionality of these systems is significantly influenced by the molecular interactions among their constituents; thus, quantitative analysis of these interactions might enhance the formulation of more effective pharmaceuticals. This review outlines the key physicochemical principles of mixed micelle formation, including thermodynamics and synergistic interactions of amphiphiles, while emphasizing their relevance in current research and practical pharmaceutical applications. Various experimental methods, such as surface tension measurement, conductometric and calorimetric tests, and spectroscopic techniques, are compared in terms of their conditions of application and performance in understanding micelle formation and micelle structure. We clearly point out that the interpretation and evaluation of the properties of colloidal systems containing drug molecules solubilized by mixed micelles and an amphiphilic drug incorporated into micelles must be discussed and evaluated separately. Understanding the limitations and characteristics of the physical/chemical principles applied is essential for the rational design of mixed micelle carriers tailored to specific therapeutic needs. Full article
(This article belongs to the Special Issue Nanotechnology in Drug Delivery: Applications and Perspectives)
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26 pages, 2485 KB  
Review
Advances in Nano-Drug Delivery Systems for Chronic Autoimmune Diseases: A Focus on Diabetes Mellitus, Inflammatory Bowel Disease, and Rheumatoid Arthritis
by Mengqing Hu, Yimiao Zhou, Lin Yang, Liquan Zhou, Xiao Liu, Tianjin Ma and Zuowei Xiao
Molecules 2026, 31(12), 2094; https://doi.org/10.3390/molecules31122094 - 14 Jun 2026
Viewed by 376
Abstract
The global prevalence of autoimmune diseases ranges from 3% to 8%, with women at a significantly higher risk than men. The core mechanisms underlying these diseases include impaired T-cell and B-cell immune tolerance, abnormal cytokine production, and aberrant activation of related signaling pathways. [...] Read more.
The global prevalence of autoimmune diseases ranges from 3% to 8%, with women at a significantly higher risk than men. The core mechanisms underlying these diseases include impaired T-cell and B-cell immune tolerance, abnormal cytokine production, and aberrant activation of related signaling pathways. Conventional treatments primarily focus on suppressing immune responses, but their efficacy remains limited and they are often associated with substantial side effects. Nanomedicine leverages nanoscale materials to enable precise diagnosis and targeted therapy. Nanocarriers can penetrate biological barriers, enhance cellular uptake, and prolong circulation time in vivo, demonstrating considerable potential for drug delivery. Common nanoscale drug delivery platforms include nanoparticles, polymeric micelles, liposomes, dendrimers, mesoporous materials, hydrogels, and exosomes. Each carrier type possesses distinct characteristics in terms of drug-loading capacity, stability, responsiveness, and biocompatibility, thereby enabling targeted delivery and controlled release. This review summarizes recent advances in nano-delivery technologies for three representative chronic autoimmune diseases: diabetes mellitus (DM), inflammatory bowel disease (IBD), and rheumatoid arthritis (RA). Nano-delivery systems can improve therapeutic outcomes by optimizing drug delivery, targeting complications, and modulating the pathological microenvironment. They enhance drug bioavailability, reduce off-target and systemic adverse effects, and provide novel strategies for the precise and efficient treatment of chronic autoimmune diseases. Full article
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16 pages, 4055 KB  
Protocol
Practical Workflow for Building Local Mass Spectral Libraries for Untargeted Metabolomics
by Torbjørn Norberg Myhre, Terkel Hansen, Tetiana Lutchyn, Marie Mardal and Terje Vasskog
Metabolites 2026, 16(6), 412; https://doi.org/10.3390/metabo16060412 (registering DOI) - 12 Jun 2026
Viewed by 186
Abstract
Background: Metabolite identification and annotation remain major bottlenecks in untargeted metabolomics because mass spectral features often lack sufficient specificity. High-confidence annotation requires experimental validation using authentic standards analyzed under matched chromatographic and ionization conditions, providing greater reliability than in silico predictions or [...] Read more.
Background: Metabolite identification and annotation remain major bottlenecks in untargeted metabolomics because mass spectral features often lack sufficient specificity. High-confidence annotation requires experimental validation using authentic standards analyzed under matched chromatographic and ionization conditions, providing greater reliability than in silico predictions or database matching alone. This study aimed to develop a practical and scalable workflow for constructing a high-quality mass spectral library using a commercially available analytical standards kit. Methods: A total of 603 metabolites from the MSMLS kit were organized into 42 mixtures, each containing approximately 15 compounds. Mixture design was based on molecular mass and distribution coefficient values, specifically logD at pH 3.1, with a minimum logD spacing of 0.15 to improve chromatographic separation and reduce co-elution. This strategy was used to minimize the total number of injections while maintaining spectral quality. The resulting spectra were evaluated against online spectral resources and in silico fragmentation predictions. A preliminary proof-of-concept analysis was also performed using human serum samples. Results: Using this workflow, 471 metabolites, corresponding to approximately 78% of the standards, were successfully detected and incorporated into the spectral library. Comparison with online resources and in silico fragmentation predictions demonstrated improved spectral quality and reliability. The proof-of-concept serum analysis enabled identification of endogenous metabolites using the constructed library. In addition, the robustness and applicability of the workflow were further supported by a method validation study using metabolites derived from this library. Conclusions: This workflow provides a scalable strategy for constructing mass spectral libraries that balances spectral quality with analytical throughput. By using rational mixture design and authentic standards analyzed under matched experimental conditions, the approach enables substantial metabolite coverage while maintaining data reliability and minimizing experimental effort. Full article
(This article belongs to the Collection Advances in Metabolomics)
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16 pages, 1079 KB  
Article
The Role of Vitamin D in Modulating the Innate Immune Response in Children with Vesicoureteral Reflux
by Marius-Cosmin Colceriu, Diana Jecan-Toader, Paul Luchian Aldea, Bogdan Bulată, Dan Delean, Alina Grama, Alexandra Mititelu, Tudor Lucian Pop, Simona Clichici, Teodora Mocan and Andreea-Liana Boț (Răchişan)
Children 2026, 13(6), 811; https://doi.org/10.3390/children13060811 - 12 Jun 2026
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Abstract
Background: Vitamin D, through its role in antimicrobial peptide (AMP) expression, may influence innate immunity and inflammation in urinary tract infections (UTIs). This study evaluated its role in patients with vesicoureteral reflux (VUR) and its contribution to the pathophysiology of reflux nephropathy [...] Read more.
Background: Vitamin D, through its role in antimicrobial peptide (AMP) expression, may influence innate immunity and inflammation in urinary tract infections (UTIs). This study evaluated its role in patients with vesicoureteral reflux (VUR) and its contribution to the pathophysiology of reflux nephropathy (RN). Methods: We conducted a cross-sectional observational study of 25 pediatric patients with VUR, representing a subgroup analysis of a larger cohort examined in a previous study. We determined patients’ vitamin D status, correlated it with recurrent UTIs and RS, and explored its relationship with urinary LL-37, NGAL, and IL-6 levels as markers of innate immune function. Results: Serum vitamin D levels ranged from 10.7 to 123.2 ng/mL (mean 39.5 ng/mL); 12% had deficiency and 20% had insufficient levels. Low vitamin D levels were detected in patients with more than five acute pyelonephritis (APNs), with a mean value classified as insufficient (27.3 ng/mL). Patients with RS had a lower mean vitamin D level compared to those without (30.51 ng/mL vs. 41.23 ng/mL), though the difference was not statistically significant (p = 0.39). No significant associations were found between vitamin D and urinary IL-6 or NGAL levels. A strong positive correlation was observed between vitamin D and urinary LL-37/creatinine (r = 0.78, r2 = 0.61). Conclusions: Vitamin D appears to influence the frequency of UTIs and the development of RS, primarily by modulating LL-37 secretion, suggesting a possible role in the pathophysiology of RN. Full article
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