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Keywords = systemic drug delivery

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29 pages, 3563 KiB  
Article
Assessment of Hydrogels for Intra-Articulate Application, Based on Sodium Hyaluronate Doped with Synthetic Polymers and Incorporated with Diclofenac Sodium
by Dorota Wójcik-Pastuszka, Maja Grabara and Witold Musiał
Int. J. Mol. Sci. 2025, 26(15), 7631; https://doi.org/10.3390/ijms26157631 (registering DOI) - 6 Aug 2025
Abstract
The intra-articular application of drugs has gained considerable interest with regard to formulations for advanced drug delivery systems. It has been identified as a potential route for local drug delivery. A drug agent is usually incorporated into the hydrogel to prolong and control [...] Read more.
The intra-articular application of drugs has gained considerable interest with regard to formulations for advanced drug delivery systems. It has been identified as a potential route for local drug delivery. A drug agent is usually incorporated into the hydrogel to prolong and control the drug release. This study aimed to design and evaluate an intra-articular hydrogel based sodium hyaluronate, which was modified with an additional polymer to enable the sustained release of the incorporated anti-inflammatory agent, diclofenac sodium (NaDic). Viscosity studies, drug release tests and FTIR−ATR measurements, as well as DSC analysis, were carried out to evaluate the obtained formulations. The viscosity measurements were performed using a rotational viscometer. The drug release was carried out by employing the apparatus paddle over the disk. The concentration of the released drug was obtained spectrophotometrically. The results revealed that the addition of the second polymer to the matrix influenced the dynamic viscosity of the hydrogels. The highest viscosity of (25.33 ± 0.55) × 103 cP was observed when polyacrylic acid (PA) was doped in the formulation. This was due to the hydrogen bond formation between both polymers. The FTIR−ATR investigations and DSC study revealed the hydrogen bond formation between the drug and both polymers. The drug was released the slowest from hydrogel doped with PA and 17.2 ± 3.7% of NaDic was transported to the acceptor fluid within 8 h. The hydrogel based on hyaluronan sodium doped with PA and containing NaDic is a promising formulation for the prolonged and controlled intra-articulate drug delivery of anti-inflammatory agents. Full article
(This article belongs to the Special Issue New Insights into Hyaluronan in Human Medicine)
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14 pages, 1215 KiB  
Article
Daptomycin-Loaded Nano-Drug Delivery System Based on Biomimetic Cell Membrane Coating Technology: Preparation, Characterization, and Evaluation
by Yuqin Zhou, Shihan Du, Kailun He, Beilei Zhou, Zixuan Chen, Cheng Zheng, Minghao Zhou, Jue Li, Yue Chen, Hu Zhang, Hong Yuan, Yinghong Li, Yan Chen and Fuqiang Hu
Pharmaceuticals 2025, 18(8), 1169; https://doi.org/10.3390/ph18081169 - 6 Aug 2025
Abstract
Background/Objective: Staphylococcus aureus (S. aureus) is a clinically significant pathogenic bacterium. Daptomycin (DAP) is a cyclic lipopeptide antibiotic used to treat infections caused by multidrug-resistant Gram-positive bacteria, including S. aureus. However, DAP currently faces clinical limitations due to its short [...] Read more.
Background/Objective: Staphylococcus aureus (S. aureus) is a clinically significant pathogenic bacterium. Daptomycin (DAP) is a cyclic lipopeptide antibiotic used to treat infections caused by multidrug-resistant Gram-positive bacteria, including S. aureus. However, DAP currently faces clinical limitations due to its short half-life, toxic side effects, and increasingly severe drug resistance issues. This study aimed to develop a biomimetic nano-drug delivery system to enhance targeting ability, prolong blood circulation, and mitigate resistance of DAP. Methods: DAP-loaded chitosan nanocomposite particles (DAP-CS) were prepared by electrostatic self-assembly. Macrophage membrane vesicles (MM) were prepared by fusion of M1-type macrophage membranes with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). A biomimetic nano-drug delivery system (DAP-CS@MM) was constructed by the coextrusion process of DAP-CS and MM. Key physicochemical parameters, including particle diameter, zeta potential, encapsulation efficiency, and membrane protein retention, were systematically characterized. In vitro immune escape studies and in vivo zebrafish infection models were employed to assess the ability of immune escape and antibacterial performance, respectively. Results: The particle size of DAP-CS@MM was 110.9 ± 13.72 nm, with zeta potential +11.90 ± 1.90 mV, and encapsulation efficiency 70.43 ± 1.29%. DAP-CS@MM retained macrophage membrane proteins, including functional TLR2 receptors. In vitro immune escape assays, DAP-CS@MM demonstrated significantly enhanced immune escape compared with DAP-CS (p < 0.05). In the zebrafish infection model, DAP-CS@MM showed superior antibacterial efficacy over both DAP and DAP-CS (p < 0.05). Conclusions: The DAP-CS@MM biomimetic nano-drug delivery system exhibits excellent immune evasion and antibacterial performance, offering a novel strategy to overcome the clinical limitations of DAP. Full article
(This article belongs to the Section Pharmaceutical Technology)
47 pages, 7003 KiB  
Review
Phthalocyanines Conjugated with Small Biologically Active Compounds for the Advanced Photodynamic Therapy: A Review
by Kyrylo Chornovolenko and Tomasz Koczorowski
Molecules 2025, 30(15), 3297; https://doi.org/10.3390/molecules30153297 - 6 Aug 2025
Abstract
Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, [...] Read more.
Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, efficacy, and multifunctionality. These conjugates combine light-activated reactive oxygen species (ROS) production with targeted delivery and controlled release, offering enhanced treatment precision and reduced off-target toxicity. Chemotherapeutic agent conjugates, including those with erlotinib, doxorubicin, tamoxifen, and camptothecin, demonstrate receptor-mediated uptake, pH-responsive release, and synergistic anticancer effects, even overcoming multidrug resistance. Beyond oncology, ZnPc conjugates with antibiotics, anti-inflammatory drugs, antiparasitics, and antidepressants extend photodynamic therapy’s scope to antimicrobial and site-specific therapies. Targeting moieties such as folic acid, biotin, arginylglycylaspartic acid (RGD) and epidermal growth factor (EGF) peptides, carbohydrates, and amino acids have been employed to exploit overexpressed receptors in tumors, enhancing cellular uptake and tumor accumulation. Fluorescent dye and porphyrinoid conjugates further enrich these systems by enabling imaging-guided therapy, efficient energy transfer, and dual-mode activation through pH or enzyme-sensitive linkers. Despite these promising strategies, key challenges remain, including aggregation-induced quenching, poor aqueous solubility, synthetic complexity, and interference with ROS generation. In this review, the examples of Pc-based conjugates were described with particular interest on the synthetic procedures and optical properties of targeted compounds. Full article
(This article belongs to the Section Organic Chemistry)
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19 pages, 13597 KiB  
Systematic Review
Current Research Trends and Hotspots in Radiotherapy Combined with Nanomaterials for Cancer Treatment: A Bibliometric and Visualization Analysis
by Muyasha Abulimiti, Shiqin Dai, Ebara Mitsuhiro, Yu Sugawara, Yinuo Li, Hideyuki Sakurai and Yoshitaka Matsumoto
Nanomaterials 2025, 15(15), 1205; https://doi.org/10.3390/nano15151205 - 6 Aug 2025
Abstract
This study investigated the evolving trends, current research hotspots, and future directions of radiotherapy combined with nanobiomaterials through a bibliometric analysis. Publications related to nanobiomaterials used in radiotherapy between 2004 and 2024 were retrieved from the Web of Science Core Collection database and [...] Read more.
This study investigated the evolving trends, current research hotspots, and future directions of radiotherapy combined with nanobiomaterials through a bibliometric analysis. Publications related to nanobiomaterials used in radiotherapy between 2004 and 2024 were retrieved from the Web of Science Core Collection database and analyzed using VOSviewer, R, and CiteSpace. China emerged as the leading contributor, accounting for 1051 publications (50.41%), followed by the USA. Liu Zhuang is the most productive author in this field. American Chemical Society (ACS) Nano published the most influential articles and accumulated the highest number of citations. Advanced Targeted Therapies in Cancer: Drug Nanocarriers, the Future of Chemotherapy was the most cited, with 1255 citations. Citation bursts have revealed emerging research trends in targeted delivery, cellular studies, co-delivery strategies, immunogenic cell death, polymeric nanoparticles, tumor research, and drug delivery systems, indicating potential avenues for future research. Over the past two decades, nanomaterials for radiotherapy have gained substantial attention. Key areas of focus include enhancing the efficacy of radiotherapy, achieving targeted drug delivery, minimizing adverse effects, and integrating nanomaterials with other therapeutic modalities. Future investigations are expected to improve the precision of radiotherapy, augment radiation effects, and optimize the tumor microenvironment. Full article
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26 pages, 3940 KiB  
Article
In Vitro Proof-of-Concept Study: Lidocaine and Epinephrine Co-Loaded in a Mucoadhesive Liquid Crystal Precursor System for Topical Oral Anesthesia
by Giovana Maria Fioramonti Calixto, Aylla Mesquita Pestana, Arthur Antunes Costa Bezerra, Marcela Tavares Luiz, Jonatas Lobato Duarte, Marlus Chorilli and Michelle Franz-Montan
Pharmaceuticals 2025, 18(8), 1166; https://doi.org/10.3390/ph18081166 - 6 Aug 2025
Abstract
Background: Local anesthesia is essential for most dental procedures, but its parenteral administration is often painful. Topical anesthetics are commonly used to minimize local anesthesia pain; however, commercial formulations fail to fully prevent the discomfort of local anesthetic injection. Methods: We developed and [...] Read more.
Background: Local anesthesia is essential for most dental procedures, but its parenteral administration is often painful. Topical anesthetics are commonly used to minimize local anesthesia pain; however, commercial formulations fail to fully prevent the discomfort of local anesthetic injection. Methods: We developed and characterized a novel lidocaine and epinephrine co-loaded liquid crystalline precursor system (LCPS) for topical anesthesia. The formulation was structurally characterized using polarized light microscopy (PLM) and small-angle X-ray scattering (SAXS). Rheological behavior was assessed through continuous and oscillatory rheological analyses. Texture profile analysis, in vitro mucoadhesive force evaluation, in vitro drug release and permeation studies, and an in vivo toxicity assay using the chicken chorioallantoic membrane (CAM) model were also conducted. Results: PLM and SAXS confirmed the transition of the LCPS from a microemulsion to a lamellar liquid crystalline structure upon contact with artificial saliva. This transition enhanced formulation consistency by over 100 times and tripled mucoadhesion strength. The LCPS also provided controlled drug release, reducing permeation flow by 93% compared to the commercial formulation. Importantly, the CAM assay indicated that the LCPS exhibited similar toxicity to the commercial product. Conclusions: The developed LCPS demonstrated promising physicochemical and biological properties for topical anesthesia, including enhanced mucoadhesion, controlled drug delivery, and acceptable biocompatibility. These findings support its potential for in vivo application and future clinical use to reduce pain during dental anesthesia procedures. Full article
(This article belongs to the Special Issue Advances in Topical and Mucosal Drug Delivery Systems)
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29 pages, 2060 KiB  
Review
Revitalizing Colchicine: Novel Delivery Platforms and Derivatives to Expand Its Therapeutic Potential
by Natallia V. Dubashynskaya, Anton N. Bokatyi, Mikhail M. Galagudza and Yury A. Skorik
Int. J. Mol. Sci. 2025, 26(15), 7591; https://doi.org/10.3390/ijms26157591 - 6 Aug 2025
Abstract
Colchicine is a potent alkaloid with well-established anti-inflammatory properties. It shows significant promise in treating classic immune-mediated inflammatory diseases, as well as associated cardiovascular diseases, including atherosclerosis. However, its clinical use is limited by a narrow therapeutic window, dose-limiting systemic toxicity, variable bioavailability, [...] Read more.
Colchicine is a potent alkaloid with well-established anti-inflammatory properties. It shows significant promise in treating classic immune-mediated inflammatory diseases, as well as associated cardiovascular diseases, including atherosclerosis. However, its clinical use is limited by a narrow therapeutic window, dose-limiting systemic toxicity, variable bioavailability, and clinically significant drug–drug interactions, partly mediated by modulation of P-glycoprotein and cytochrome P450 3A4 metabolism. This review explores advanced delivery strategies designed to overcome these limitations. We critically evaluate lipid-based systems, such as solid lipid nanoparticles, liposomes, transferosomes, ethosomes, and cubosomes; polymer-based nanoparticles; microneedles; and implants, including drug-eluting stents. These systems ensure targeted delivery, improve pharmacokinetics, and reduce toxicity. Additionally, we discuss chemical derivatization approaches, such as prodrugs, codrugs, and strategic ring modifications (A-, B-, and C-rings), aimed at optimizing both the efficacy and safety profile of colchicine. Combinatorial nanoformulations that enable the co-delivery of colchicine with synergistic agents, such as glucocorticoids and statins, as well as theranostic platforms that integrate therapeutic and diagnostic functions, are also considered. These innovative delivery systems and derivatives have the potential to transform colchicine therapy by broadening its clinical applications while minimizing adverse effects. Future challenges include scalable manufacturing, long-term safety validation, and the translation of research into clinical practice. Full article
(This article belongs to the Section Macromolecules)
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14 pages, 5990 KiB  
Article
Distinctive Features of the Buffer Capacity of Polyelectrolyte Microcapsules Formed on MnCO3 Core
by Aleksandr L. Kim, Alexey V. Dubrovskii and Sergey A. Tikhonenko
Polymers 2025, 17(15), 2149; https://doi.org/10.3390/polym17152149 - 6 Aug 2025
Abstract
The development of layer-by-layer polyelectrolyte microcapsules (PMCs) with defined buffer capacity (BC) is a key task for creating stable systems in biomedicine and materials science. Manganese carbonate (MnCO3), which shares properties with CaCO3 and the ability to form hollow structures, [...] Read more.
The development of layer-by-layer polyelectrolyte microcapsules (PMCs) with defined buffer capacity (BC) is a key task for creating stable systems in biomedicine and materials science. Manganese carbonate (MnCO3), which shares properties with CaCO3 and the ability to form hollow structures, represents a promising alternative. However, its interaction with polyelectrolytes and its influence on BC remain insufficiently studied. This research focuses on determining the BC of PMCs templated on MnCO3 cores under varying ionic strength (0.22–3 M NaCl) and temperature (60–90 °C), as well as comparing the results with PMCs templated on CaCO3 and PS cores. It was found that MnCO3-based PMCs (PMCMn) exhibit hybrid behavior between CaCO3- and PS-based PMCs: the BC dynamics of PMCMn and CaCO3-based PMCs (PMCCa) in water are identical. At different ionic strength at pH < 5, the BC of PMCMn and PS-based PMCs (PMCPS) remains unchanged, while at pH > 8.5, the BC of PMCMn increases only at 3 M NaCl. The BC of PMCMn remains stable under heating, whereas the BC of PMCCa and PMCPS decreases. These results confirm that the choice of core material dictates PMC functionality, paving the way for adaptive systems in biosensing and controlled drug delivery. Full article
(This article belongs to the Special Issue Stimuli-Responsive Polymers: Advances and Prospects)
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23 pages, 1970 KiB  
Review
Resveratrol as a Therapeutic Agent in Alzheimer’s Disease: Evidence from Clinical Studies
by Nidhi Puranik, Meenakshi Kumari, Shraddha Tiwari, Thakur Dhakal and Minseok Song
Nutrients 2025, 17(15), 2557; https://doi.org/10.3390/nu17152557 - 5 Aug 2025
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and neuronal dysfunction. It is driven by the accumulation of amyloid-beta (Aβ) plaques, Tau protein hyperphosphorylation, oxidative stress, and neuroinflammation. Resveratrol (RSV) is a natural polyphenolic compound found in [...] Read more.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and neuronal dysfunction. It is driven by the accumulation of amyloid-beta (Aβ) plaques, Tau protein hyperphosphorylation, oxidative stress, and neuroinflammation. Resveratrol (RSV) is a natural polyphenolic compound found in grapes, berries, and red wine that has garnered attention for its potential neuroprotective properties in combating AD. The neuroprotective effects of RSV are mediated through the activation of sirtuins (SIRT1), inhibition of Aβ aggregation, modulation of Tau protein phosphorylation, and the attenuation of oxidative stress and inflammatory responses. RSV also enhances mitochondrial function and promotes autophagy, which are important processes for maintaining neuronal health. Preclinical studies have demonstrated its efficacy in reducing Aβ burden, improving cognitive performance, and mitigating synaptic damage; however, challenges such as poor bioavailability, rapid metabolism, and limited blood–brain barrier penetration restrict its clinical applicability. Recent technological advances and selected modifications are being explored to overcome these limitations and enhance its therapeutic efficacy. This review summarizes the multifaceted neuroprotective mechanisms of RSV, the synergistic potential of natural compounds in enhancing neuroprotection, and the advancements in formulation strategies aimed at mitigating AD pathology. Leveraging the therapeutic potential of natural compounds represents a compelling paradigm shift for AD management, paving the way for future clinical applications. Full article
(This article belongs to the Special Issue The Neuroprotective Activity of Natural Dietary Compounds)
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33 pages, 1598 KiB  
Review
Research Strategies and Methods of Hydrogels for Antitumor Drug Delivery
by Tianjiao Zeng, Lusi Chen, Toru Yoshitomi, Naoki Kawazoe, Yingnan Yang and Guoping Chen
Biomedicines 2025, 13(8), 1899; https://doi.org/10.3390/biomedicines13081899 - 4 Aug 2025
Abstract
Tumor treatments have substantially advanced through various approaches, including chemotherapy, radiotherapy, immunotherapy, and gene therapy. However, efficient treatment necessitates overcoming physiological barriers that impede the delivery of therapeutic agents to target sites. Drug delivery systems (DDSs) are a prominent research area, particularly in [...] Read more.
Tumor treatments have substantially advanced through various approaches, including chemotherapy, radiotherapy, immunotherapy, and gene therapy. However, efficient treatment necessitates overcoming physiological barriers that impede the delivery of therapeutic agents to target sites. Drug delivery systems (DDSs) are a prominent research area, particularly in tumor therapy. This review provides a comprehensive overview of hydrogel-based DDSs for tumor treatment, focusing on the strategies and designs of DDSs based on the unique pathophysiological characteristics of tumors. The design and preparation of hydrogel systems for DDSs are summarized and highlighted. The challenges and opportunities for translating hydrogel-based DDSs into clinical applications are discussed. Full article
(This article belongs to the Section Drug Discovery, Development and Delivery)
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41 pages, 1115 KiB  
Review
Resveratrol as a Novel Therapeutic Approach for Diabetic Retinopathy: Molecular Mechanisms, Clinical Potential, and Future Challenges
by Snježana Kaštelan, Suzana Konjevoda, Ana Sarić, Iris Urlić, Ivana Lovrić, Samir Čanović, Tomislav Matejić and Ana Šešelja Perišin
Molecules 2025, 30(15), 3262; https://doi.org/10.3390/molecules30153262 - 4 Aug 2025
Abstract
Diabetic retinopathy (DR) is a progressive, multifactorial complication of diabetes and one of the major global causes of visual impairment. Its pathogenesis involves chronic hyperglycaemia-induced oxidative stress, inflammation, mitochondrial dysfunction, neurodegeneration, and pathological angiogenesis, as well as emerging systemic contributors such as gut [...] Read more.
Diabetic retinopathy (DR) is a progressive, multifactorial complication of diabetes and one of the major global causes of visual impairment. Its pathogenesis involves chronic hyperglycaemia-induced oxidative stress, inflammation, mitochondrial dysfunction, neurodegeneration, and pathological angiogenesis, as well as emerging systemic contributors such as gut microbiota dysregulation. While current treatments, including anti-vascular endothelial growth factor (anti-VEGF) agents, corticosteroids, and laser photocoagulation, have shown clinical efficacy, they are largely limited to advanced stages of DR, require repeated invasive procedures, and do not adequately address early neurovascular and metabolic abnormalities. Resveratrol (RSV), a naturally occurring polyphenol, has emerged as a promising candidate due to its potent antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic properties. This review provides a comprehensive analysis of the molecular mechanisms by which RSV exerts protective effects in DR, including modulation of oxidative stress pathways, suppression of inflammatory cytokines, enhancement of mitochondrial function, promotion of autophagy, and inhibition of pathological neovascularisation. Despite its promising pharmacological profile, the clinical application of RSV is limited by poor aqueous solubility, rapid systemic metabolism, and low ocular bioavailability. Various routes of administration, including intravitreal injection, topical instillation, and oral and sublingual delivery, have been investigated to enhance its therapeutic potential. Recent advances in drug delivery systems, including nanoformulations, liposomal carriers, and sustained-release intravitreal implants, offer potential strategies to address these challenges. This review also explores RSV’s role in combination therapies, its potential as a disease-modifying agent in early-stage DR, and the relevance of personalised medicine approaches guided by metabolic and genetic factors. Overall, the review highlights the therapeutic potential and the key translational challenges in positioning RSV as a multi-targeted treatment strategy for DR. Full article
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15 pages, 2179 KiB  
Review
From Nutrition to Innovation: Biomedical Applications of Egg Components
by Amin Mohseni Ghalehghazi and Wen Zhong
Molecules 2025, 30(15), 3260; https://doi.org/10.3390/molecules30153260 - 4 Aug 2025
Abstract
Valued for their nutritional content, eggs have recently gained attention as a versatile biomaterial owing to their biocompatibility, biodegradability, and unique structural and biochemical composition. This review highlights the biomedical potential of various egg components—eggshell, eggshell membrane, egg white, and egg yolk—and their [...] Read more.
Valued for their nutritional content, eggs have recently gained attention as a versatile biomaterial owing to their biocompatibility, biodegradability, and unique structural and biochemical composition. This review highlights the biomedical potential of various egg components—eggshell, eggshell membrane, egg white, and egg yolk—and their applications in bone grafting, tissue engineering, wound healing, drug delivery, and biosensors. Eggshells serve as a natural, calcium-rich source for bone tissue engineering and regenerative medicine. The eggshell membrane, with its antimicrobial and structural properties, offers promise as a wound healing scaffold. Egg white, known for its gelation and film-forming capabilities, is utilized in hydrogel-based systems for drug delivery and biosensing. Egg yolk, rich in lipids and immunoglobulin Y (IgY) antibodies, is being explored for diagnostic and therapeutic applications. This review critically examines the advantages and limitations of each egg-derived component and outlines current research gaps, offering insights into future directions for the development of egg-based biomaterials in biomedical engineering. Full article
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30 pages, 7811 KiB  
Article
Preparation and Characterization of Cyperus-Derived Exosomes Loaded with Selenium Nanoparticles for Selenium Delivery Based on Exosome Protein Quantitation
by Dexiu Zhao, Xiaojun Yang, Abulimiti Kelimu, Bin Wu, Weicheng Hu, Hongbo Fan, Lei Jing, Dongmei Yang and Xinhong Huang
Foods 2025, 14(15), 2724; https://doi.org/10.3390/foods14152724 - 4 Aug 2025
Viewed by 60
Abstract
Appropriate carriers or templates are crucial for maintaining the stability, biological activity, and bioavailability of selenium nanoparticles (SeNPs). Selecting suitable templates remains challenging for fully utilizing SeNPs functionalities and developing applicable products. Exosome-like nanoparticles (ELNs) have gained importance in drug delivery systems, yet [...] Read more.
Appropriate carriers or templates are crucial for maintaining the stability, biological activity, and bioavailability of selenium nanoparticles (SeNPs). Selecting suitable templates remains challenging for fully utilizing SeNPs functionalities and developing applicable products. Exosome-like nanoparticles (ELNs) have gained importance in drug delivery systems, yet research on selenium products prepared using exosomes remains limited. To address this gap, we utilized Cyperus bean ELNs to deliver SeNPs, investigated three preparation methods for SeNPs-ELNs, identified the optimal approach, and performed characterization studies. Notably, all three methods successfully loaded SeNPs. Ultrasonic cell fragmentation is the optimal approach, achieving significant increases in selenium loading (5.59 ± 0.167 ng/μg), enlargement of particle size (431.17 ± 10.78 nm), and reduced absolute zeta potential (−4.1 ± 0.43 mV). Moreover, both exosome formulations demonstrated enhanced stability against aggregation during storage at 4 °C, while their stability varied with pH conditions. In vitro digestibility tests showed greater stability of SeNP-ELNs in digestive fluids compared to ELNs alone. Additionally, neither ELNs nor SeNP-ELNs exhibited cytotoxicity toward LO2 cells, and the relative erythrocyte hemolysis remained below 5% at protein concentrations of 2.5, 7.5, 15, 30, and 60 μg/mL. Overall, ultrasonic cell fragmentation effectively loaded plant-derived exosomes with nano-selenium at high capacity, presenting new opportunities for their use as functional components in food and pharmaceutical applications. Full article
(This article belongs to the Section Food Nutrition)
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17 pages, 432 KiB  
Article
Anomalous Drug Transport in Biological Tissues: A Caputo Fractional Approach with Non-Classical Boundary Modeling
by Ahmed Ghezal, Ahmed A. Al Ghafli and Hassan J. Al Salman
Fractal Fract. 2025, 9(8), 508; https://doi.org/10.3390/fractalfract9080508 - 4 Aug 2025
Viewed by 101
Abstract
This paper focuses on the numerical modeling of drug diffusion in biological tissues using fractional time-dependent parabolic equations with non-local boundary conditions. The model includes a Caputo fractional derivative to capture the non-local effects and memory inherent in biological processes, such as drug [...] Read more.
This paper focuses on the numerical modeling of drug diffusion in biological tissues using fractional time-dependent parabolic equations with non-local boundary conditions. The model includes a Caputo fractional derivative to capture the non-local effects and memory inherent in biological processes, such as drug absorption and transport. The theoretical framework of the problem is based on the work of Alhazzani, et al.,which demonstrates the solution’s goodness, existence, and uniqueness. Building on this foundation, we present a robust numerical method designed to deal with the complexity of fractional derivatives and non-local interactions at the boundaries of biological tissues. Numerical simulations reveal how fractal order and non-local boundary conditions affect the drug concentration distribution over time, providing valuable insights into drug delivery dynamics in biological systems. The results underscore the potential of fractal models to accurately represent diffusion processes in heterogeneous and complex biological environments. Full article
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32 pages, 2710 KiB  
Review
Polyphosphazene-Based Nanotherapeutics
by Sara Gutierrez-Gutierrez, Rocio Mellid-Carballal, Noemi Csaba and Marcos Garcia-Fuentes
J. Funct. Biomater. 2025, 16(8), 285; https://doi.org/10.3390/jfb16080285 - 2 Aug 2025
Viewed by 262
Abstract
Poly(organo)phosphazenes (PPZs) are increasingly recognized as versatile biomaterials for drug delivery applications in nanomedicine. Their unique hybrid structure—featuring an inorganic backbone and highly tunable organic side chains—confers exceptional biocompatibility and adaptability. Through precise synthetic methodologies, PPZs can be engineered to exhibit a wide [...] Read more.
Poly(organo)phosphazenes (PPZs) are increasingly recognized as versatile biomaterials for drug delivery applications in nanomedicine. Their unique hybrid structure—featuring an inorganic backbone and highly tunable organic side chains—confers exceptional biocompatibility and adaptability. Through precise synthetic methodologies, PPZs can be engineered to exhibit a wide spectrum of functional properties, including the formation of multifunctional nanostructures tailored for specific therapeutic needs. These attributes enable PPZs to address several critical challenges associated with conventional drug delivery systems, such as poor pharmacokinetics and pharmacodynamics. By modulating solubility profiles, enhancing drug stability, enabling targeted delivery, and supporting controlled release, PPZs offer a robust platform for improving therapeutic efficacy and patient outcomes. This review explores the fundamental chemistry, biopharmaceutical characteristics, and biomedical applications of PPZs, particularly emphasizing their role in zero-dimensional nanotherapeutic systems, including various nanoparticle formulations. PPZ-based nanotherapeutics are further examined based on their drug-loading mechanisms, which include electrostatic complexation in polyelectrolytic systems, self-assembly in amphiphilic constructs, and covalent conjugation with active pharmaceutical agents. Together, these strategies underscore the potential of PPZs as a next-generation material for advanced drug delivery platforms. Full article
(This article belongs to the Special Issue Nanomaterials for Drug Targeting and Drug Delivery (2nd Edition))
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20 pages, 11379 KiB  
Article
Silk Fibroin–Alginate Aerogel Beads Produced by Supercritical CO2 Drying: A Dual-Function Conformable and Haemostatic Dressing
by Maria Rosaria Sellitto, Domenico Larobina, Chiara De Soricellis, Chiara Amante, Giovanni Falcone, Paola Russo, Beatriz G. Bernardes, Ana Leite Oliveira and Pasquale Del Gaudio
Gels 2025, 11(8), 603; https://doi.org/10.3390/gels11080603 - 2 Aug 2025
Viewed by 233
Abstract
Infection control and bleeding management in deep wounds remain urgent and unmet clinical challenges that demand innovative, multifunctional, and sustainable solutions. Unlike previously reported sodium alginate and silk fibroin-based gel formulations, the present work introduces a dual-functional system combining antimicrobial and haemostatic activity [...] Read more.
Infection control and bleeding management in deep wounds remain urgent and unmet clinical challenges that demand innovative, multifunctional, and sustainable solutions. Unlike previously reported sodium alginate and silk fibroin-based gel formulations, the present work introduces a dual-functional system combining antimicrobial and haemostatic activity in the form of conformable aerogel beads. This dual-functional formulation is designed to absorb exudate, promote clotting, and provide localized antimicrobial action, all essential for accelerating wound repair in high-risk scenarios within a single biocompatible system. Aerogel beads were obtained by supercritical drying of a silk fibroin–sodium alginate blend, resulting in highly porous, spherical structures measuring 3–4 mm in diameter. The formulations demonstrated efficient ciprofloxacin encapsulation (42.75–49.05%) and sustained drug release for up to 12 h. Fluid absorption reached up to four times their weight in simulated wound fluid and was accompanied by significantly enhanced blood clotting, outperforming a commercial haemostatic dressing. These findings highlight the potential of silk-based aerogel beads as a multifunctional wound healing platform that combines localized antimicrobial delivery, efficient fluid and exudate management, biodegradability, and superior haemostatic performance in a single formulation. This work also shows for the first time how the prilling encapsulation technique with supercritical drying is able to successfully produce silk fibroin and sodium alginate composite aerogel beads. Full article
(This article belongs to the Special Issue Aerogels and Composites Aerogels)
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