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Keywords = enzyme-loaded nanoparticles

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13 pages, 7740 KB  
Article
Trimethyl Chitosan-Engineered Cod Skin Peptide Nanosystems Alleviate Behavioral and Cognitive Deficits in D-Galactose-Induced Alzheimer’s Disease Model Mice
by Songzhi Kong, Lijiao Lv, Jiaqi Guo, Guiping Lu, Dongdong Li and Xin Zhou
Mar. Drugs 2025, 23(12), 472; https://doi.org/10.3390/md23120472 - 10 Dec 2025
Viewed by 413
Abstract
Alzheimer’s disease (AD) is a common neurodegenerative disorder with limited effective treatments. Cod skin collagen peptides (CSCPs) have neuroprotective potential for AD but face poor bioavailability—due to gastrointestinal enzyme cleavage and hepatic first-pass metabolism—prompting this study to develop a nanodelivery system to enhance [...] Read more.
Alzheimer’s disease (AD) is a common neurodegenerative disorder with limited effective treatments. Cod skin collagen peptides (CSCPs) have neuroprotective potential for AD but face poor bioavailability—due to gastrointestinal enzyme cleavage and hepatic first-pass metabolism—prompting this study to develop a nanodelivery system to enhance CSCPs’ efficacy. Trimethyl chitosan (TMC)-based CSCP-loaded nanoparticles (CSCPs-NPs) were synthesized via ionic gelation, characterized for physicochemical properties, and tested in a D-galactose-induced AD mouse model (six groups: normal control, model, CSCPs low/high dose, blank NPs, CSCPs-NPs) using behavioral tests, histopathology, immunohistochemistry, and ELISA. CSCPs-NPs had a hydrodynamic diameter of 93.25 ± 21.52 nm, polydispersity index of 0.18 ± 0.13, 61.17% encapsulation efficiency, and sustained 24 h release. In AD mice, CSCPs-NPs significantly improved cognitive function and motor coordination, reduced hippocampal atrophy, preserved neurons, and mitigated oxidative stress, neuroinflammation, and apoptosis (upregulated Bcl-2, downregulated Bax)—effects matching high-dose free CSCPs. This TMC-based nanoformulation enhances CSCPs’ bioavailability and provides a promising strategy for AD intervention. Full article
(This article belongs to the Section Marine Pharmacology)
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28 pages, 19684 KB  
Article
Carvacrol-Loaded Chitosan Nanoparticles as a Multifunctional Nanotherapeutic Strategy Targeting Oxidative Stress, Inflammation, Apoptosis, and Genotoxicity in Nonalcoholic Fatty Liver Disease
by M. Alfawaz, Ekramy M. Elmorsy, Ahmad Najem Alshammari, Noor A. Hakim, Najlaa M. M. Jawad, Soha A. Hassan, Manal S. Fawzy and Safya E. Esmaeel
Antioxidants 2025, 14(12), 1432; https://doi.org/10.3390/antiox14121432 - 28 Nov 2025
Viewed by 520
Abstract
Nonalcoholic fatty liver disease (NAFLD) associated with high-fat diet (HFD) intake involves oxidative stress, inflammation, apoptosis, and genotoxicity. Carvacrol, a natural monoterpenoid phenol, exhibits potent antioxidant, anti-inflammatory, and cytoprotective properties, but its clinical application is limited by poor solubility and bioavailability. Chitosan nanoparticles, [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) associated with high-fat diet (HFD) intake involves oxidative stress, inflammation, apoptosis, and genotoxicity. Carvacrol, a natural monoterpenoid phenol, exhibits potent antioxidant, anti-inflammatory, and cytoprotective properties, but its clinical application is limited by poor solubility and bioavailability. Chitosan nanoparticles, known for their biocompatibility and ability to enhance drug delivery, offer a promising nanotherapeutic platform for carvacrol delivery in NAFLD. Given the limited therapeutic options for NAFLD, there is a growing interest in nanotherapeutic strategies to enhance the delivery and efficacy of natural antioxidants. This study examined carvacrol-loaded chitosan nanoparticles (CRV-CNPs) in HFD-induced NAFLD. Sixty rats were assigned to six groups: control, CRV-treated (100 mg/kg), CRV-CNP-treated (100 mg/kg), HFD-fed, and two combination groups receiving HFD with either CRV or CRV-CNPs (100 mg/kg) for six weeks after 14 weeks on HFD. Liver function, metabolic markers, oxidative stress parameters, antioxidant enzyme levels, inflammatory and fibrotic mediators, apoptotic gene expression, genotoxicity indices, and histopathological changes were evaluated. CRV-CNPs showed greater efficacy than free carvacrol in ameliorating hepatic dysfunction and metabolic disturbances in HFD-fed rats. CRV-CNPs significantly reduced malondialdehyde, upregulated Nrf2, and elevated hepatic glutathione peroxidase, superoxide dismutase, catalase, and reduced glutathione. Inflammatory markers (NF-κB, iNOS, IL-1β, CRP) and transforming growth factor-beta were suppressed. Pro-apoptotic genes (Bax, Caspase-3) were downregulated, while antiapoptotic Bcl-2 was upregulated. CRV-CNPs also reduced DNA fragmentation and 8-hydroxy-2′-deoxyguanosine levels, indicating strong antigenotoxic effects. Histopathological and ultrastructural assessments revealed mitigated steatosis, preserved hepatic architecture, and maintained mitochondrial integrity. In conclusion, CRV-CNPs provide potent hepatoprotection by targeting oxidative stress, inflammation, apoptosis, and genotoxicity in NAFLD, demonstrating enhanced bioavailability, solubility, and sustained release, which support their potential as an advanced nanotherapeutic strategy for NAFLD management. Full article
(This article belongs to the Special Issue Applications of Antioxidant Nanoparticles, 2nd Edition)
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20 pages, 4347 KB  
Article
Synergistic Stabilization of Horseradish Peroxidase by Green-Synthesized Silver-Decorated Magnetite Nanoparticles: Toward Sustainable Enzyme Technology
by Laila S. Alqarni, Yaaser Q. Almulaiky, Elham N. Bifari and Reda M. El-Shishtawy
Catalysts 2025, 15(12), 1098; https://doi.org/10.3390/catal15121098 - 21 Nov 2025
Viewed by 775
Abstract
In this study, silver-decorated magnetite nanoparticles (Ag@Fe3O4) were synthesized via a green method using Brachychiton populneus leaf extract and employed as an efficient support matrix for immobilization of horseradish peroxidase (HRP). The biosynthesized nanocomposite exhibited magnetic properties that facilitated [...] Read more.
In this study, silver-decorated magnetite nanoparticles (Ag@Fe3O4) were synthesized via a green method using Brachychiton populneus leaf extract and employed as an efficient support matrix for immobilization of horseradish peroxidase (HRP). The biosynthesized nanocomposite exhibited magnetic properties that facilitated easy separation and reuse, while the silver loading imparted enhanced stability and potential antimicrobial activity. Comprehensive physicochemical characterizations, including XRD, FTIR, FESEM, EDX, BET, and VSM, confirmed the successful formation of Ag@Fe3O4 and effective enzyme loading. The immobilization yield of HRP on Ag@Fe3O4 reached 93%, and the immobilized enzyme showed improved tolerance toward temperature and pH variations, with an optimal pH of 7.5 and optimal temperature of 60 °C, compared to 7.0 and 50 °C for the free enzyme. Kinetic studies revealed a moderate increase in Km but maintained or slightly increased Vmax, indicating preserved catalytic efficiency. The immobilized enzyme demonstrated excellent reusability over 15 cycles (66% residual activity) and long-term storage stability (81% activity after 60 days at 4 °C). These enhancements are attributed to the protective microenvironment provided by the Ag@Fe3O4 matrix, which mitigates denaturation and leaching. This work highlights the potential of Ag@Fe3O4 as a sustainable and reusable platform for enzyme immobilization in biocatalytic applications, particularly in environmental remediation and industrial bioprocessing. Full article
(This article belongs to the Special Issue Green Chemistry and Catalysis, 2nd Edition)
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24 pages, 5216 KB  
Article
MOF-Engineered Platelet-Mimicking Nanocarrier-Encapsulated Cascade Enzymes for ROS Scavenging and Anti-Inflammation in Cerebral Ischemia–Reperfusion Injury
by Hao Li, Xiaowei Xie, Yu Zhang, Xiaopeng Han, Ting Shi, Jiayin Li, Wanyu Chen, Qin Wei, Hong Pan, Shuxian Xu, Qiuyu Chen, Lifang Yin and Chao Qin
Pharmaceutics 2025, 17(11), 1478; https://doi.org/10.3390/pharmaceutics17111478 - 16 Nov 2025
Viewed by 617
Abstract
Background/Objectives: Cerebral ischemia–reperfusion injury (CIRI) remains a major challenge in the treatment of ischemic stroke, characterized by intertwined oxidative stress and neuroinflammation. Existing monotherapies often fail to address this dual pathology effectively. We developed PLSCZ, a biomimetic nanoplatform integrating a catalytic core of [...] Read more.
Background/Objectives: Cerebral ischemia–reperfusion injury (CIRI) remains a major challenge in the treatment of ischemic stroke, characterized by intertwined oxidative stress and neuroinflammation. Existing monotherapies often fail to address this dual pathology effectively. We developed PLSCZ, a biomimetic nanoplatform integrating a catalytic core of imidazolate framework-8 (ZIF-8)-encapsulated superoxide dismutase (SOD) and catalase (CAT) enzymes with a hybrid platelet membrane shell. This design strategically employs metal–organic frameworks (MOFs) to effectively overcome the critical limitations of enzyme instability and provide a cascade catalytic environment, while the biomimetic surface modification enhances targeting capability, thereby enabling dual-pathway intervention against CIRI. Methods: PLSCZ was engineered by co-encapsulating SOD and CAT within a ZIF-8 core to form a cascade antioxidant system (SCZ). The core was further coated with a hybrid membrane composed of rapamycin-loaded phospholipids and natural platelet membranes. The nanoparticle was characterized by size, structure, enzyme activity, and targeting capability. In vitro and in vivo efficacy was evaluated using oxygen–glucose deprivation/reoxygenation (OGD/R) models and a transient middle cerebral artery occlusion/reperfusion (tMCAO/r) rat model. Results: In vitro, PLSCZ exhibited enhanced enzymatic stability and cascade catalytic efficiency, significantly scavenging reactive oxygen species (ROS) and restoring mitochondrial function. The platelet membrane conferred active targeting to ischemic brain regions and promoted immune evasion. PLSCZ effectively polarized microglia toward the anti-inflammatory M2 phenotype, reduced pro-inflammatory cytokine levels, restored autophagic flux, and preserved blood–brain barrier integrity. In vivo, in tMCAO/r rats, PLSCZ markedly targeted the ischemic hemisphere, reduced infarct volume, improved neurological function, and attenuated neuroinflammation. Conclusions: By synergistic ROS scavenging and anti-inflammatory action, the PLSCZ nanozyme overcomes the limitations of conventional monotherapies for CIRI. This biomimetic, multi-functional platform effectively reduces oxidative stress, modulates the phenotype of microglia, decreases infarct volume, and promotes neurological recovery, offering a promising multi-mechanistic nanotherapeutic for CIRI and a rational design model for MOF-based platforms. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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24 pages, 4208 KB  
Article
Nanoparticle-Based Delivery of Resveratrol Suppresses Ehrlich Ascites Carcinoma and Protects Testicular Function via Antioxidant, Anti-Angiogenic, Anti-Inflammatory, and Pro-Apoptotic Mechanisms
by M. Alfawaz, Ekramy M. Elmorsy, Ahmad Najem Alshammari, Marwa Nagy Emam, Islam Ibrahim Hegab, Aly A. M. Shaalan, Manal S. Fawzy and Lina Abdelhady Mohammed
Biomolecules 2025, 15(11), 1605; https://doi.org/10.3390/biom15111605 - 15 Nov 2025
Viewed by 758
Abstract
This study, for the first time, evaluated the therapeutic potential of resveratrol-loaded phytosome nanoparticles (RES-PNPs) against Ehrlich ascites carcinoma (EAC) and associated testicular dysfunction, compared with free resveratrol (RES). Ninety male Swiss albino mice were divided into six groups, (1) control; (2) RES [...] Read more.
This study, for the first time, evaluated the therapeutic potential of resveratrol-loaded phytosome nanoparticles (RES-PNPs) against Ehrlich ascites carcinoma (EAC) and associated testicular dysfunction, compared with free resveratrol (RES). Ninety male Swiss albino mice were divided into six groups, (1) control; (2) RES (10 mg/kg/day, orally); (3) RES-PNPs (10 mg/kg/day, orally); (4) EAC, induced by intraperitoneal injection of 2.5 × 106 cells; (5) EAC + RES; and (6) EAC + RES-PNPs, treated for 20 days post-tumor inoculation. Tumor growth parameters, reproductive function, antioxidant enzyme activities, inflammatory mediators, apoptotic markers, and histopathological features were assessed. Additionally, in silico docking was performed to identify molecular targets mediating RES effects. RES-PNPs markedly reduced tumor volume, ascitic cell viability, and body weight gain while significantly prolonging survival compared with free RES. Molecular assays revealed enhanced pro-apoptotic signaling (increased Bax and Caspase-3, decreased Bcl-2), suppression of vascular endothelial growth factor (VEGF), and inhibition of COX-2 with reduced TNF-α, IFN-γ, and IL-1β levels. RES-PNPs also restored semen quality, normalized reproductive hormones, elevated antioxidant enzyme activities, and reduced lipid and protein oxidation, corroborated by notable testicular histological protection. In conclusion, Resveratrol-loaded phytosome nanoparticles provide superior anti-tumor, antioxidant, anti-inflammatory, and pro-apoptotic benefits compared with free RES. These findings highlight RES-PNPs as a potent and stable nanoformulation for effective EAC suppression and preservation of male reproductive integrity. Full article
(This article belongs to the Special Issue The Role of Nanoparticles in Tumor Treatment)
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16 pages, 17098 KB  
Article
Facile Preparation of High-Performance Non-Enzymatic Glucose Sensors Based on Au/CuO Nanocomposites
by Lian Ma, Tao Wang, Hao Mei, Yuhao You, Zhandong Lin, Weishuang Li, Bojie Li, Silin Kang and Lei Zhu
Catalysts 2025, 15(11), 1020; https://doi.org/10.3390/catal15111020 - 30 Oct 2025
Viewed by 504
Abstract
Non-enzymatic glucose sensing has attracted considerable interest as a promising alternative to enzyme-based sensors, addressing limitations such as poor stability and high cost. To overcome the challenges of expensive noble metals and the inherent issues of pure copper oxide (CuO), including low conductivity [...] Read more.
Non-enzymatic glucose sensing has attracted considerable interest as a promising alternative to enzyme-based sensors, addressing limitations such as poor stability and high cost. To overcome the challenges of expensive noble metals and the inherent issues of pure copper oxide (CuO), including low conductivity and aggregation tendency, this study developed a composite sensing material based on two-dimensional CuO nanosheets decorated with gold nanoparticles (Au NPs). A series of Au/CuO nanocomposites with varying Au loadings were synthesized through a combined hydrothermal and in situ reduction approach. Systematic electrochemical characterization revealed that the composite with 7.41 wt% Au loading exhibited optimal sensing performance, achieving sensitivities of 394.29 and 257.14 μA·mM−1·cm−2 across dual linear ranges of 5–3550 μM and 4550–11,550 μM, respectively, with a detection limit of 10 μM and a rapid response time of 3 s. The sensor also demonstrated selectivity against common interferents as well as long-term stability. This work highlights the importance of precise noble metal loading control in optimizing sensor performance and offers a feasible material design strategy for developing high-performance non-enzymatic glucose sensors. Full article
(This article belongs to the Special Issue Heterogeneous Catalysis in China: New Horizons and Recent Advances)
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17 pages, 1686 KB  
Article
Solid Lipid Nanoparticles by Coacervation from Natural Soaps: Preliminary Studies for Oral Delivery of an Insulin Analogue
by Annalisa Bozza, Arianna Marengo, Federica Blua, Elisabetta Marini, Stefano Bagatella, Elena Ugazio, Elisabetta Muntoni and Luigi Battaglia
Pharmaceutics 2025, 17(10), 1261; https://doi.org/10.3390/pharmaceutics17101261 - 26 Sep 2025
Viewed by 739
Abstract
Background/Objectives: Oral insulin continues to constitute a challenge due to its low uptake by the gut wall and degradation by gastrointestinal proteolytic enzymes. Such concerns might be surmounted by means of nanoparticle delivery. Methods: In this study, glargine insulin has been [...] Read more.
Background/Objectives: Oral insulin continues to constitute a challenge due to its low uptake by the gut wall and degradation by gastrointestinal proteolytic enzymes. Such concerns might be surmounted by means of nanoparticle delivery. Methods: In this study, glargine insulin has been loaded into solid lipid nanoparticles prepared via coacervation from Shea and Mango soaps, due to hydrophobic ion pairing. Subsequently, ex vivo tied-up-gut experiments were performed with fluorescently labeled peptide. Additionally, re-dispersible oral solid dosage forms (powders and tablets) were obtained from nanoparticle suspensions via freeze-drying and spray-drying. Results: Solid lipid nanoparticles are capable of enhancing peptide permeation into different gut sections. Furthermore, spray-drying permits the preparation, which can be scaled up, of a re-dispersible powder from the nanoparticle suspension. Conclusions: This engineered process is suitable for the formulation of solid oral dosage forms, such as granulates and tablets, and presents promising potential for oral insulin delivery, paving the way for the assessment of its pharmacological efficacy in further in vivo studies. Full article
(This article belongs to the Special Issue Recent Advances in Peptide and Protein-Based Drug Delivery Systems)
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24 pages, 5800 KB  
Article
Differential Effects of Chitosan–Salicylic Acid Nanocomposite and Salicylic Acid on Cucumber Mosaic Virus in Cucumber
by Sherif Mohamed El-Ganainy, Radwa M. Shafie, Ahmed M. Soliman, Amira A. Mazyad, Muhammad Naeem Sattar, Hosny H. Kesba, Biju V. Chellappan and Khaled Yehia Farroh
Polymers 2025, 17(16), 2195; https://doi.org/10.3390/polym17162195 - 11 Aug 2025
Cited by 2 | Viewed by 1542
Abstract
Cucumber mosaic virus (CMV) is a destructive viral pathogen of vegetables, fruits, grains, and ornamentals across the globe. This study investigated the comparative antiviral efficacy of chitosan–salicylic acid nanocomposite (Ch/SA NC) and salicylic acid (SA) against CMV in cucumber plants. Transmission electron microscopy [...] Read more.
Cucumber mosaic virus (CMV) is a destructive viral pathogen of vegetables, fruits, grains, and ornamentals across the globe. This study investigated the comparative antiviral efficacy of chitosan–salicylic acid nanocomposite (Ch/SA NC) and salicylic acid (SA) against CMV in cucumber plants. Transmission electron microscopy (TEM) analyses revealed that Ch/SA NCs can aggregate on the viral coat protein surface, suggesting direct nanoparticle–virus interaction. Greenhouse trials showed that Ch/SA NC, particularly at 90 ppm applied 24 h before CMV inoculation, was the most effective treatment in reducing disease severity and viral load. SA at the same concentration also conferred significant protection when used prophylactically. An RT-PCR analysis confirmed suppression or complete silencing of CMV coat protein gene expression, especially Ch/SA NC-treated plants. Both treatments significantly enhanced the physiological condition of infected plants, including restoration of chlorophyll a, chlorophyll b, and carotenoids, and elevated levels of total phenolics, flavonoids carbohydrates, and proteins. In addition, they boosted the key antioxidant enzymes activities (POX, PPO, SOD) and improved vegetative growth indicators such as plant height, fruit fresh weight, and number of fruits per plant. These results indicate that Ch/SA NC and SA not only inhibit CMV replication but also stimulate host defense responses, improving overall plant health. The strong antiviral effect is likely due to the dual action of Ch/SA NC: direct virus binding and induction of systemic acquired resistance (SAR). Given their efficacy and eco-friendly nature, especially the Ch/SA NC, these treatments offer a promising strategy for integrated viral disease management. Future studies should investigate long-term environmental safety, molecular mechanisms, and field-level applicability. Full article
(This article belongs to the Special Issue Biobased and Biodegradable Polymer Blends and Composites II)
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26 pages, 2898 KB  
Article
Phytochemical Characterization, Bioactivities, and Nanoparticle-Based Topical Gel Formulation Development from Four Mitragyna speciosa Varieties
by Pimporn Anantaworasakul, Weeraya Preedalikit, Phunsuk Anantaworasakul, Sudarshan Singh, Aekkhaluck Intharuksa, Warunya Arunotayanun, Mingkwan Na Takuathung, Songwut Yotsawimonwat and Chuda Chittasupho
Gels 2025, 11(7), 494; https://doi.org/10.3390/gels11070494 - 26 Jun 2025
Cited by 1 | Viewed by 2010
Abstract
Mitragyna speciosa (kratom) is a traditional medicinal plant rich in bioactive alkaloids and phenolics, known for their antioxidant and anti-aging properties. This study aimed to develop nanoparticle-based topical gels from ethanolic extracts of four kratom varieties, including Kan Daeng (KD), Hang Kang (HK), [...] Read more.
Mitragyna speciosa (kratom) is a traditional medicinal plant rich in bioactive alkaloids and phenolics, known for their antioxidant and anti-aging properties. This study aimed to develop nanoparticle-based topical gels from ethanolic extracts of four kratom varieties, including Kan Daeng (KD), Hang Kang (HK), Tai Bai-yao (KY), and Kan Keaw (KG). Kratom NPs were prepared using a solvent displacement method. The resulting nanoparticles (NPs) exhibited sizes of 201.9–256.2 nm, polydispersity indices (PDI) below 0.3, and a zeta potential between −22.6 and −29.6 mV. The phytochemical analysis revealed that KG and KY extracts contained the highest total phenolic content (TPC) and total flavonoid content (TFC), which were mostly retained after NP formulation. The HPLC analysis confirmed HK as the richest source of mitragynine (9.97 ± 0.10% w/w), while NP formulations displayed slightly reduced levels. Antioxidant activities assessed by DPPH, ABTS, and FRAP assays revealed enhanced radical scavenging in nanoparticle formulations, with IC50 values ranging from 151.23 to 199.87 µg/mL (DPPH) and 207.37 to 272.83 µg/mL (ABTS). All formulations exhibited a significant inhibition of collagenase (80.56 ± 1.60 to 97.23 ± 0.29%), elastase (45.46 ± 6.53 to 52.19 ± 1.20%), and hyaluronidase (83.23 ± 2.34 to 91.67 ± 3.56%), with nanoparticle forms showing superior enzyme inhibition. Notably, nanoparticle formulations exhibited superior inhibitory effects compared to crude extracts. HaCaT cytotoxicity tests confirmed high biocompatibility (IC50 > 700 µg/mL), especially for KD and KG NPs. The NP-loaded gels demonstrated acceptable physicochemical stability after heating/cooling cycle testing, with pH (7.27 to 7.88), viscosity (10.719 to 12.602 Pa·s), and favorable visual and textural properties. In summary, KG and KY cultivars emerged as the most promising cosmeceutical candidates due to their superior phytochemical content, antioxidant capacity, enzyme-inhibitory activities, and formulation performance. These findings support the potential use of KG NP and KY NP-loaded gels as multifunctional cosmeceutical agents for antioxidant protection, anti-aging, and skin rejuvenation. Full article
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34 pages, 3547 KB  
Review
A Review of Silica-Based Nanoplatforms for Anticancer Cargo Delivery
by Andrea Mosseri, Leticia Sanchez-Uriel, Jose I. Garcia-Peiro, Felipe Hornos and Jose L. Hueso
Int. J. Mol. Sci. 2025, 26(12), 5850; https://doi.org/10.3390/ijms26125850 - 18 Jun 2025
Cited by 2 | Viewed by 2737
Abstract
Stimuli-responsive silica nanoparticles have emerged as a promising platform for the targeted and controlled delivery of therapeutic agents in cancer therapy. These nanoparticles possess unique physicochemical properties that allow for the stimuli-triggered release of loaded cargos, such as drugs, enzymes, oligonucleotides, photosensitizers, and [...] Read more.
Stimuli-responsive silica nanoparticles have emerged as a promising platform for the targeted and controlled delivery of therapeutic agents in cancer therapy. These nanoparticles possess unique physicochemical properties that allow for the stimuli-triggered release of loaded cargos, such as drugs, enzymes, oligonucleotides, photosensitizers, and metals. The stimuli-responsive nature of these nanoparticles enables them to respond to specific internal and external signals within the tumor microenvironment, including pH, temperature, and redox potential, among others. This leads to the enhanced targeting of cancer cells and improved therapeutic efficacy while minimizing the off-target effects. This review highlights recent advances in the development and application of stimuli-responsive silica nanoparticles for the delivery of multiple active agents for cancer therapy. Overall, stimuli-responsive silica nanoparticles offer great potential for the development of more effective cancer therapies with improved selectivity and reduced side effects. Full article
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16 pages, 4566 KB  
Article
Fucoxanthin-Loaded Solid Lipid Nanoparticles Exert Potent Therapeutic Efficacy in Combating High-Fat Diet Induced Obesity in Mice
by Lijun Ding, Xiao Luo and Weijia Wen
Int. J. Mol. Sci. 2025, 26(11), 5249; https://doi.org/10.3390/ijms26115249 - 29 May 2025
Cited by 3 | Viewed by 2041
Abstract
Obesity and associated metabolic disorders pose significant health challenges. Fucoxanthin, a lipophilic compound, has shown promising anti-obesity potential, but its poor solubility and bioavailability limit therapeutic efficacy. The successful formulation of solid lipid nanoparticles (SLNs) amplified fucoxanthin’s efficacy in mitigating obesity and the [...] Read more.
Obesity and associated metabolic disorders pose significant health challenges. Fucoxanthin, a lipophilic compound, has shown promising anti-obesity potential, but its poor solubility and bioavailability limit therapeutic efficacy. The successful formulation of solid lipid nanoparticles (SLNs) amplified fucoxanthin’s efficacy in mitigating obesity and the associated metabolic dysregulation. High-fat diet (HFD)-induced obese mice were treated with free fucoxanthin, lyophilized SLNs (L-SLN), and dispersed SLNs (D-SLN) loaded with fucoxanthin. The intervention with D-SLN demonstrated the most significant reduction in body weight gain (29.94%) and fat mass gain (61.80%) compared to the HFD group (p < 0.05), alongside notable improvements in metabolic indicators including fasting blood glucose, liver enzymes, lipid profile, and inflammatory markers such as leptin and monocyte chemoattractant protein 1 (MCP-1) levels. Histopathological evaluation corroborated these findings, showing highly reduced hepatic lipid droplet accumulation and improved adipocyte and testicular morphology. This advancement paved the way for translating fucoxanthin into a clinically effective anti-obesity agent. Full article
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19 pages, 9476 KB  
Review
Development of Liquid Chromatography on Monolithic Supports—From First Concepts to Real Analytical and Preparative Techniques
by Tomislav Friganović and Djuro Josić
Int. J. Mol. Sci. 2025, 26(10), 4695; https://doi.org/10.3390/ijms26104695 - 14 May 2025
Cited by 2 | Viewed by 2080
Abstract
In this review, we trace the evolution of liquid chromatography from the pioneering work of Tennikova and Svec to the current monolithic polymethacrylate supports for performing liquid chromatography with biological macromolecules and nanoparticles, which offer rapid, high-throughput separations. By using interconnected channels with [...] Read more.
In this review, we trace the evolution of liquid chromatography from the pioneering work of Tennikova and Svec to the current monolithic polymethacrylate supports for performing liquid chromatography with biological macromolecules and nanoparticles, which offer rapid, high-throughput separations. By using interconnected channels with a tailored channel diameter, monoliths minimize the diffusion limitations typical of particle-based systems. Radial flow designs and optimized channel architectures enable the direct loading of complex biological fluids, reducing the need for sample preparation and optimizing the purification of large biomolecules and nanoparticles such as proteins, nucleic acids, extracellular vesicles, and viruses. Recent work has integrated monoliths into immunoaffinity and enzyme reactor platforms, streamlining analytical workflows and preparative applications in vaccine production and gene therapy. The ongoing advances in monolithic materials, channel geometry, and continuous processing hold promise for even greater efficiency and scalability in future applications. Full article
(This article belongs to the Section Biochemistry)
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24 pages, 4202 KB  
Article
Resveratrol-Loaded Solid Lipid Nanoparticles Reinforced Hyaluronic Hydrogel: Multitarget Strategy for the Treatment of Diabetes-Related Periodontitis
by Raffaele Conte, Anna Valentino, Fabrizia Sepe, Francesco Gianfreda, Roberta Condò, Loredana Cerroni, Anna Calarco and Gianfranco Peluso
Biomedicines 2025, 13(5), 1059; https://doi.org/10.3390/biomedicines13051059 - 27 Apr 2025
Cited by 9 | Viewed by 2276
Abstract
Background/Objectives: Periodontitis and diabetes mellitus share a well-established bidirectional relationship, where hyperglycemia exacerbates periodontal inflammation, and periodontal disease further impairs glycemic control. Within the diabetic periodontal microenvironment, an imbalance between pro-inflammatory (M1) and anti-inflammatory (M2) macrophages promotes chronic inflammation, oxidative stress, delayed healing, [...] Read more.
Background/Objectives: Periodontitis and diabetes mellitus share a well-established bidirectional relationship, where hyperglycemia exacerbates periodontal inflammation, and periodontal disease further impairs glycemic control. Within the diabetic periodontal microenvironment, an imbalance between pro-inflammatory (M1) and anti-inflammatory (M2) macrophages promotes chronic inflammation, oxidative stress, delayed healing, and alveolar bone resorption. Resveratrol (RSV), a polyphenol with antioxidant, anti-inflammatory, and pro-osteogenic properties, holds potential to restore macrophage balance. However, its clinical application is limited by poor bioavailability and instability. This study aimed to develop and evaluate a novel RSV delivery system to overcome these limitations and promote periodontal tissue regeneration under diabetic conditions. Methods: A drug delivery system comprising RSV-loaded solid lipid nanoparticles embedded within a cross-linked hyaluronic acid hydrogel (RSV@CLgel) was formulated. The system was tested under hyperglycemic and inflammatory conditions for its effects on macrophage polarization, cytokine expression, oxidative stress, mitochondrial function, and osteoblast differentiation. Results: RSV@CLgel effectively suppressed pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) while upregulating anti-inflammatory markers (IL-10, TGF-β). It significantly reduced oxidative stress by decreasing ROS and lipid peroxidation levels and improved mitochondrial function and antioxidant enzyme activity. Furthermore, RSV@CLgel enhanced osteoblast differentiation, as evidenced by increased ALP activity, calcium nodule formation, and upregulation of osteogenic genes (COL-I, RUNX2, OCN, OPN). It also inhibited RANKL-induced osteoclastogenesis, contributing to alveolar bone preservation. Conclusions: The RSV@CLgel delivery system presents a promising multifunctional strategy for the management of diabetic periodontitis. By modulating immune responses, reducing oxidative stress, and promoting periodontal tissue regeneration, RSV@CLgel addresses key pathological aspects of diabetes-associated periodontal disease. Full article
(This article belongs to the Special Issue Periodontal Disease and Periodontal Tissue Regeneration)
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14 pages, 5530 KB  
Article
Intranasal Application of Foxp3 Introduced with Poly(d,l-lactic-co-glycolic acid) (PLGA) Nanoparticles (Foxp3 NPs) Attenuates Allergic Inflammation in a Mouse Model of Allergic Rhinitis
by Seung Cheol Han, Sunhee Yeon, Hyejeen Kim and Sookyoung Park
Pharmaceutics 2025, 17(5), 575; https://doi.org/10.3390/pharmaceutics17050575 - 27 Apr 2025
Cited by 2 | Viewed by 1065
Abstract
Background: Allergic rhinitis (AR) is a common disease that requires more convenient, safe, and effective therapy. This study aimed to investigate the therapeutic effect of Forkhead box protein3 (Foxp3) introduced with poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (Foxp3 NPs) in [...] Read more.
Background: Allergic rhinitis (AR) is a common disease that requires more convenient, safe, and effective therapy. This study aimed to investigate the therapeutic effect of Forkhead box protein3 (Foxp3) introduced with poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (Foxp3 NPs) in an AR mouse model. Methods: A murine model of allergic rhinitis was established using BALB/c mice through initial sensitization by intraperitoneal administration of ovalbumin (OVA), followed by repeated intranasal OVA challenges. Foxp3 plasmid-loaded PLGA nanoparticles were subsequently administered via either the intranasal or intraperitoneal route to evaluate therapeutic efficacy. Episodes of sneezing and nose rubbing were counted. The serum total IgE, OVA-specific IgE, and cytokine levels in nasal lavage fluid (NALF) were determined by ELISA (Enzyme-Linked ImmunoSorbent Assay). Nasal mucosa from each group were analyzed using protein, reverse transcriptase–polymerase chain reaction (RT-PCR), and histological analyses. Result: Rubbing and sneezing symptoms improved in the Foxp3 NPs intranasal administration group. Foxp3 NPs intranasal administration markedly ameliorated OVA-induced nasal allergic inflammation. The total IgE and OVA-specific IgE serum level and IL-4, IL-13 expression levels of NALF were significantly decreased in the treated Foxp3 NPs group. The histopathological results of nasal mucosa were also normal, with no cellular infiltration and no inflammation in the Foxp3 NPs group. Conclusions: These results suggest that Foxp3 NPs alleviate nasal allergic inflammation and may have therapeutic value in the treatment of AR. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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14 pages, 2594 KB  
Article
Comparison of Drying Techniques to Produce Stable and Bioavailable Encapsulated ACE-2 Nanoparticles
by Yigong Guo, Alberto Baldelli, Dai Shi, David D. Kitts, Anubhav Pratap-Singh and Anika Singh
Pharmaceutics 2025, 17(4), 537; https://doi.org/10.3390/pharmaceutics17040537 - 21 Apr 2025
Viewed by 875
Abstract
Background/Objectives: COVID-19 infection continues globally, with frequent emergence of unfamiliar SARS-CoV-2 variants acting to impair immunity. The competitive binding of SARS-CoV-2 spike proteins and angiotensin-converting enzyme 2 (ACE-2) can decrease the binding of the virus on native ACE-2 receptors on healthy human cells. [...] Read more.
Background/Objectives: COVID-19 infection continues globally, with frequent emergence of unfamiliar SARS-CoV-2 variants acting to impair immunity. The competitive binding of SARS-CoV-2 spike proteins and angiotensin-converting enzyme 2 (ACE-2) can decrease the binding of the virus on native ACE-2 receptors on healthy human cells. It remains a practical approach to lessen viral spread. In this study, a method to encapsulate ACE-2 in the form of chitosan/tripolyphosphate cross-linked nanoparticles (NPs) was developed with emphasis placed on the best dehydration method to secure functional ACE-2 nanoparticles. Methods: Methods: Preparation conditions were assessed by varying pH (4.0–6.5) and the ratio between chitosan and ACE-2 mixing ratios (1:1, 1.5:1, 2:1, 2.5:1, and 3:1). The formulated NPs were then dehydrated using different approaches that included spray-drying (SD), freeze-drying (FD), and spray-freeze drying (SFD) and used varying mannitol concentrations (0, 1:1, and 5:1 of total weight). The mannitol was served as a cryoprotectant in this study. Results: The best formulation achieved used a pH 5.5 with a mixing chitosan–ACE-2 ratio of 2:1, where ACE-2-loaded NPs had an average particle size of 303.7 nm, polydispersity index (PDI) of 0.21, encapsulation efficiency (EE) of 98.4%, and ACE-2 loading content (LC) of 28.4%. After reconstitution, all SD samples had a relatively low yield rate, but the ACE-2 NPs dehydrated specifically using SFD required a lower amount of added mannitol (1:1 of its total weight) and produced a higher yield rate (p < 0.05) and similar PDI and EE values, along with relatively good particle size and LC. This formulation also produced a high ACE-2 release and uptake in differentiated Caco-2 cells, thus representing an effective ACE-2 encapsulation procedure for use with dry powders. Conclusions: This work showed that spray-freeze drying was the best method to dehydrate ACE-2 NPs, using less cryoprotectant to create a significant advantage in terms of greater loading capacity with lower additive requirements. Full article
(This article belongs to the Special Issue Advances in Delivery of Peptides and Proteins)
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