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25 pages, 3376 KB  
Article
Intravenous Everolimus Formulation (Sapu003) for Clinical Trials
by Sheng-Hao Min, Kevin Forero, William Putnam, Jonathan Anderson, Robert Hoff, John Lopp, Vuong Trieu, Kwun Ho and Cynthia Lee
Int. J. Mol. Sci. 2026, 27(13), 5775; https://doi.org/10.3390/ijms27135775 (registering DOI) - 26 Jun 2026
Abstract
Everolimus is approved for the treatment of advanced renal cell carcinoma after VEGF-targeted therapy, metastatic HR-positive/HER2-negative breast cancer in combination with exemestane, and other oncologic indications. However, an intravenous option has not been developed, largely due to its pronounced hydrophobicity and limited oral [...] Read more.
Everolimus is approved for the treatment of advanced renal cell carcinoma after VEGF-targeted therapy, metastatic HR-positive/HER2-negative breast cancer in combination with exemestane, and other oncologic indications. However, an intravenous option has not been developed, largely due to its pronounced hydrophobicity and limited oral bioavailability of approximately 15–20%. In this study, we report the development of Sapu003, a novel intravenous Everolimus7 formulation enabled through the Deciparticle™ platform. A diverse library of mPEG-based block copolymers was evaluated for their ability to encapsulate Everolimus and self-assemble into stable nanoparticle structures. mPEG-Chol was ultimately selected based on its favorable biocompatibility characteristics. In addition to Everolimus, mPEG-Chol and related analogs demonstrated broad formulation compatibility with multiple hydrophobic therapeutics, including Sirolimus, Tacrolimus, Cyclosporine, as well as representative peptides and polyketides. Clinical manufacturing was conducted in a cGMP environment over a 7-day production cycle. Production was carried out under amber light using light-protective vials to reduce drug degradation. The bulk material was sterile-filtered, and subsequent fill/finish/lyophilization operations were performed under temperature-controlled conditions with high precision in fill accuracy (≥98%). After reconstitution, the final product yielding uniform Deciparticles™ that met predefined sterility and particle size criteria. Stability studies demonstrated that the formulation remained stable for at least one month at 5 °C and retained acceptable in-use stability for at least 24 h at room temperature. The process was successfully scaled beyond 10 g, supporting an ongoing Phase 1b open-label dose escalation clinical study of Sapu003 in combination with exemestane in patients with advanced mTOR-sensitive solid tumors (NCT07369505). In vivo evaluation demonstrated strong antitumor efficacy following intravenous administration (QW × 3), with tumor growth inhibition reaching 97–98% in the U-87MG glioblastoma xenograft model. No evidence of phlebitis was observed with repeated tail vein dosing. In this model, Sapu003 dosed weekly showed superior tumor suppression compared with oral Everolimus. Collectively, screening of a mPEG-block copolymer library identified mPEG-Chol as a lead excipient capable of consistently forming stable Deciparticles™ with sub-20 nm mean particle size. The resulting intravenous Everolimus formulation demonstrated scalable manufacturing, favorable stability, and potent antitumor activity in preclinical models, supporting further clinical evaluation of Sapu003 in advanced solid tumors. Full article
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24 pages, 10198 KB  
Article
Brain-Targeted 5-ALA-CAT Liposomes (BACL) Alleviate Hypoxia and Enhance Photodynamic Therapy in a Murine Glioblastoma Flank Xenograft Model via Angiopep-2-Mediated Targeting
by Qian Zhang, Yuhang Li, Jiahui Zhang, Xuewen Zhao, Danlu Li, Wenting Zhao, Xin Hai, Xin Chen, Xinlei Yang, Jingxin Gou, Chunpeng Zhang, Xing Tang and Yilei Zhao
Pharmaceutics 2026, 18(7), 777; https://doi.org/10.3390/pharmaceutics18070777 - 25 Jun 2026
Abstract
Background/Objectives: Glioblastoma multiforme (GBM) treatment is limited by tumor hypoxia and poor specificity of therapeutic agents. To address these challenges, we developed brain-targeted liposomes co-encapsulating 5-aminolevulinic acid (5-ALA) and catalase (CAT), termed brain-targeted 5-ALA-CAT liposomes (BACL), which were surface-modified with the Angiopep-2 ligand [...] Read more.
Background/Objectives: Glioblastoma multiforme (GBM) treatment is limited by tumor hypoxia and poor specificity of therapeutic agents. To address these challenges, we developed brain-targeted liposomes co-encapsulating 5-aminolevulinic acid (5-ALA) and catalase (CAT), termed brain-targeted 5-ALA-CAT liposomes (BACL), which were surface-modified with the Angiopep-2 ligand to enhance blood–brain barrier penetration and achieve multimodal therapy combining targeted delivery and oxygen generation. Methods: BACL was prepared and characterized. Tumor targeting was verified by flow cytometry and in vivo imaging. In vitro antitumor activity was evaluated by wound-healing assay, colony formation assay, live/dead staining, MTT assay, and Western blotting. In vivo efficacy, apoptosis, and safety were assessed in a subcutaneous xenograft model. Transcriptome sequencing and qRT-PCR were employed to identify molecular mechanisms and novel targets. Results: BACL exhibited favorable physicochemical properties (size: 122.4 nm, PDI: 0.189, zeta potential: −12.3 mV) and spherical morphology as observed by TEM, with encapsulation efficiencies of 51.2% for 5-ALA and 43.8% for CAT. Compared with unmodified 5-ALA, BACL increased the cellular uptake efficiency by 1.6-fold in glioma cells while maintaining catalytic stability for sustained oxygen generation. In vitro experiments demonstrated that BACL significantly inhibited glioma cell migration, colony formation, and cell viability, and induced apoptosis. In a subcutaneous xenograft tumor model, BACL-mediated photodynamic therapy (PDT) achieved a tumor growth inhibition rate of 52%, with apoptosis induction via regulation of Bcl-2, Bax, and p53 expression, and no obvious toxicity to major organs was observed. Transcriptomic analysis combined with qRT-PCR validation revealed that BACL activates multiple antitumor signaling pathways, including targeted inhibition of IL-10 and CXCL13 to disrupt cytokine–receptor interactions, as well as coordinated regulation of S100A3 and IGSF-9 expression to suppress glioma progression. Conclusions: These multimodal actions enhanced PDT efficacy while remodeling the tumor microenvironment. Our findings position BACL as a promising therapeutic platform integrating targeted delivery, hypoxia alleviation, and immunomodulation for GBM therapy. Full article
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18 pages, 3320 KB  
Article
Design, Synthesis, and Proof-of-Concept Bioassay of an Encapsulated mRNA for Human Growth Hormone
by Carolina Rivera Santiago, Andrés Quintanar Stephano and Hugo A. Barrera Saldaña
Curr. Issues Mol. Biol. 2026, 48(7), 647; https://doi.org/10.3390/cimb48070647 - 23 Jun 2026
Viewed by 74
Abstract
Background: Human growth hormone (hGH) deficiency (GHD) is typically treated with daily injections of recombinant human growth hormone (rhGH), which do not fully replicate physiological secretion patterns. This study evaluates a novel approach using synthetic mRNA encoding hGH encapsulated in lipid nanoparticles (LNPs) [...] Read more.
Background: Human growth hormone (hGH) deficiency (GHD) is typically treated with daily injections of recombinant human growth hormone (rhGH), which do not fully replicate physiological secretion patterns. This study evaluates a novel approach using synthetic mRNA encoding hGH encapsulated in lipid nanoparticles (LNPs) and designated VTRC-01 to enable endogenous hormone production. Methods: VTRC-01 was administered intramuscularly to hypophysectomized (Hypox) prepubertal Wistar rats, and its efficacy was compared with rhGH. A cohort of healthy rats was included to assess anabolic effects and safety. Results: VTRC-01 stimulated longitudinal growth in both Hypox and healthy rats, achieving effects comparable to rhGH. Treatment induced a significant anabolic response that exceeded the basal growth rate of healthy controls. Conclusions: These findings provide proof-of-concept for hGH mRNA-based therapy as a promising alternative to rhGH. Further improvements in mRNA and LNP technologies are expected to enhance safe hormone production. These promising results underscore the potential of reprogramming via therapeutic mRNA the synthesis of key endocrine regulators (such as hGH) directly within the organism, offering for the first time a powerful pathway for the potential treatment for endocrine therapies targeting growth hormone deficiency. Full article
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23 pages, 17391 KB  
Article
Metformin and cRGDfc-Modified Nanoparticles Loaded with Curcumin for Age-Related Macular Degeneration: In Vitro Pharmacodynamics and Molecular Mechanisms
by Juan Liu, Ziheng Wang, Yuchang Yang, Lisha Yi, Shiman Li, Jingyi Gao, Jia Zhou, Nannan Cheng, Xingbin Yin, Xiaoxv Dong, Jian Ni and Changhai Qu
Pharmaceutics 2026, 18(6), 761; https://doi.org/10.3390/pharmaceutics18060761 - 22 Jun 2026
Viewed by 190
Abstract
Objectives: This study aimed to develop curcumin nanoparticles (Cur@PCL-PEG-MF/cRGDfc) with retinal-targeting capability and to evaluate their biological effects and pharmacological mechanisms in vitro. Methods: After synthesis of the carrier framework, metformin (MF) and cRGDfc were conjugated to the carrier material using the carbodiimide [...] Read more.
Objectives: This study aimed to develop curcumin nanoparticles (Cur@PCL-PEG-MF/cRGDfc) with retinal-targeting capability and to evaluate their biological effects and pharmacological mechanisms in vitro. Methods: After synthesis of the carrier framework, metformin (MF) and cRGDfc were conjugated to the carrier material using the carbodiimide method and Michael addition reaction, respectively. Subsequently, self-assembled nanoparticles were formed from the carrier and curcumin under specific conditions. The materials were characterized by spectroscopy, chromatography, elemental analysis, energy-dispersive spectroscopy and X-ray diffraction. The efficacy of the formulation was evaluated in two cell lines, ARPE-19 and HUVEC-T1. In addition, the pharmacological mechanism was explored using transcriptome sequencing as a complementary approach. Key Findings: Self-assembled nanoparticles were successfully prepared by combining the two modified carrier materials, PCL-PEG-MF and PCL-PEG-cRGDfc, with curcumin. The nanoparticles exhibited an encapsulation efficiency of 78.09%, a particle size of 162.33 nm, and a zeta potential of −23.28 mV and displayed a spherical morphology. They showed sustained release in simulated physiological conditions and stronger affinity for ARPE-19 cells under oxidative stress. Nearly 100% of the nanoparticles were internalized by the cells, which was accompanied by reduced ROS and LDH release and decreased DNA fragmentation. In addition, the nanoparticles inhibited neovascularization by reducing VEGF-A release, thereby potentially protecting the retina in macular degeneration and reducing choroidal hemorrhage. Further analyses showed that curcumin and its nanoformulations significantly reduced the expression of inflammatory factors such as IL-1β and IL-18, lowered the protein levels of Caspase-1, GSDMD-N, and NLRP3, and increased AMPK levels. Conclusions: Using PCL-PEG as the carrier framework, MF and cRGDfc were conjugated to construct a curcumin-loaded nanoparticle with retinal-targeting capability. This nanoparticle, characterized by a small particle size, sustained release, and targeted delivery to retinal pigment epithelium (RPE) cells under oxidative stress, alleviated oxidative stress-induced damage. Its therapeutic effect may be mediated, at least in part, by interference with the AMPK/mTOR pathway and activation of the NLRP3/Caspase-1/GSDMD pathway. Full article
(This article belongs to the Special Issue Ocular Drug Delivery Systems and Formulations)
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35 pages, 1649 KB  
Review
The Application of Radiolabeled Mesoporous Silica Nanoparticles in Molecular Imaging
by Aleksandra Lis, Martyna Orłoś and Paweł Szymański
Molecules 2026, 31(12), 2181; https://doi.org/10.3390/molecules31122181 - 22 Jun 2026
Viewed by 230
Abstract
In medicine, nanoparticles are used for various purposes, including theranostics, imaging, diagnostics, drug delivery, tissue regeneration and targeted cancer treatments, and to minimize the harmful side effects associated with conventional therapies. Target-specific biomolecules, such as silica nanoparticles (SiNPs) labeled with metallic radionuclides, are [...] Read more.
In medicine, nanoparticles are used for various purposes, including theranostics, imaging, diagnostics, drug delivery, tissue regeneration and targeted cancer treatments, and to minimize the harmful side effects associated with conventional therapies. Target-specific biomolecules, such as silica nanoparticles (SiNPs) labeled with metallic radionuclides, are becoming increasingly popular. The choice of radionuclide is based on its nuclear properties. Silica has several advantages for nanoparticle synthesis, including high biocompatibility, the capacity for drug encapsulation due to its porous structure, and the potential for extensive surface functionalization, including radiolabeling for imaging and therapeutic applications. A radionuclide can be attached to a silica nanoparticle either directly or through the use of chelators or polymers. Additionally, the capability to encapsulate therapeutic agents within such systems offers significant potential for the development of targeted therapies. This study aims to provide a comprehensive overview of recent developments in the radiolabeling of silica-based nanoparticles, with a focus on their application in nuclear medicine, particularly in diagnostic imaging and targeted radionuclide therapy. Theranostics employs a range of imaging modalities to guide and monitor therapeutic interventions. Principal techniques include positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and Optical Imaging (such as fluorescence and bioluminescence). These imaging methods enable precise visualization of pathological sites, facilitate tracking of therapeutic agent distribution, and permit real-time assessment of treatment efficacy. Full article
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19 pages, 2819 KB  
Article
Zinc-Doped Calcium Phosphate Nanoagonists Amplifies cGAS-STING Signaling for Boosting Pyroptosis-Induced Cancer Immunotherapy
by Bangliu Yang, Xinyu Li, Mingyue Zhang, Shiyao Guo, Xueqian Wang, Peiran Chen, Dongqin Yu, Chao Qi and Kaiyong Cai
J. Funct. Biomater. 2026, 17(6), 308; https://doi.org/10.3390/jfb17060308 - 22 Jun 2026
Viewed by 344
Abstract
The combination of chemotherapy and immunotherapy represents a promising approach that leverages their complementary benefits. However, the side effects resulting from off-target effects and the low efficiency of immune activation remain a significant concern. Herein, we developed a zinc-doped calcium phosphate (ZCP) nanocarrier [...] Read more.
The combination of chemotherapy and immunotherapy represents a promising approach that leverages their complementary benefits. However, the side effects resulting from off-target effects and the low efficiency of immune activation remain a significant concern. Herein, we developed a zinc-doped calcium phosphate (ZCP) nanocarrier for the delivery of the chemotherapeutic drug doxorubicin (DOX). By further encapsulating whole proteins from 4T1 breast cancer cells, we constructed a novel nanodrug delivery system named ZCPDM. This system enables specific targeting of tumor cells and undergoes intracellular degradation to release DOX, Zn2+, and Ca2+. As a chemotherapeutic agent, DOX induces apoptosis while significantly elevating intracellular reactive oxygen species (ROS), thereby enhancing cytotoxicity. This leads to DNA damage and the release of chromosomal fragments. These DNA fragments, together with Zn2+, activate the cGAS-STING signaling pathway and trigger pyroptosis, which promotes more efficient recognition and clearance of tumor cells by the immune system. Through these dual mechanisms, ZCPDM effectively combines chemotherapy and immunotherapy. The anti-tumor efficacy and underlying mechanisms were validated at the cellular level. Furthermore, studies in tumor-bearing mice demonstrated its robust anti-tumor performance and ability to suppress tumor recurrence, along with good biosafety. This targeted drug delivery system achieves safe and synergistic chemo-immunotherapy through homologous targeting-mediated pyroptosis and activation of the cGAS-STING pathway, offering a novel and promising strategy for cancer treatment. Full article
(This article belongs to the Section Biomaterials for Cancer Therapies)
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56 pages, 8337 KB  
Review
Electrospun Nanofibers for Antimicrobial Therapy: From Polymer Design to Controlled Drug Release
by Andrei Teodor Matei, Oana Cramariuc, Irina Negut and Iuliana Gabriela Lupu
Coatings 2026, 16(6), 736; https://doi.org/10.3390/coatings16060736 (registering DOI) - 20 Jun 2026
Viewed by 139
Abstract
The rapid emergence of antimicrobial resistance has intensified the need for advanced therapeutic platforms capable of improving the efficacy, stability, and targeted delivery of antimicrobial agents. Electrospun nanofibers have emerged as highly promising materials for biomedical applications due to their large surface area, [...] Read more.
The rapid emergence of antimicrobial resistance has intensified the need for advanced therapeutic platforms capable of improving the efficacy, stability, and targeted delivery of antimicrobial agents. Electrospun nanofibers have emerged as highly promising materials for biomedical applications due to their large surface area, high porosity, tunable morphology, and ability to incorporate a broad range of bioactive compounds. This review provides a comprehensive overview of the design, fabrication, and biomedical applications of electrospun bioactive nanofibers functionalized with antimicrobial drugs. It presents the main nanofiber fabrication techniques, with particular emphasis on electrospinning and the influence of solution, process, and environmental parameters on fiber morphology and drug-loading efficiency. Natural, synthetic, and hybrid polymer systems commonly employed in electrospun antimicrobial nanofibers are analyzed in relation to their physicochemical properties, biocompatibility, and therapeutic performance. In addition, the review highlights different drug incorporation strategies, including encapsulation, immobilization, and surface coating, as well as the mechanisms of action of antimicrobial agents. Recent advances in nanotechnology-based antimicrobial systems and their role in overcoming analytical, biopharmaceutical, and drug-delivery limitations are also examined. Furthermore, the review addresses current challenges related to scalability, reproducibility, stability, and clinical translation of electrospun nanofibers. Finally, future perspectives focusing on multifunctional, stimuli-responsive, and personalized antimicrobial nanofiber systems are discussed as promising directions for combating bacterial infections and reducing the global burden of antimicrobial resistance. Full article
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22 pages, 2339 KB  
Article
A Novel Herbal Nano-Based Ear Drop with Ocimum gratissimum Essential Oil: An Alternative Strategy for Managing Otomycosis
by Bac V. G. Nguyen, Hoai Thu Le, Tien-Trung Dao, Quy-Nguyen Doan, Duc-Huy Pham, Nghi Bao Nguyen, Minh-Tri Le, Du-Thien Nguyen and Phuoc-Vinh Nguyen
Pharmaceutics 2026, 18(6), 751; https://doi.org/10.3390/pharmaceutics18060751 - 18 Jun 2026
Viewed by 319
Abstract
Background/Objectives: Otomycosis is a recurrent fungal infection of the external auditory canal. This disease is difficult to manage with current antifungal agents due to irritation, ototoxicity risk, and emerging resistance. Natural essential oils have been proposed as alternatives, yet their clinical application [...] Read more.
Background/Objectives: Otomycosis is a recurrent fungal infection of the external auditory canal. This disease is difficult to manage with current antifungal agents due to irritation, ototoxicity risk, and emerging resistance. Natural essential oils have been proposed as alternatives, yet their clinical application in otic formulations remains limited due to their poor solubility and stability. In this study, we report the first ear-drop formulation combining microemulsified Ocimum gratissimum essential oil and acetic acid for otomycosis treatment. Methods: The essential oil was quality-validated with eugenol content superior to 60%. A systematic formulation study was performed, and the Tween 20/isopropanol (4:1, w/w) mixture was selected as the optimal surfactant system, yielding a stable microemulsion with high encapsulation efficiency (~98%) and relevant physicochemical stability (up to 28 days). The final formulation containing 1% acetic acid and 0.3% micro-emulsified essential oil met pharmacopeial requirements in terms of appearance, pH, viscosity, and microbial limits. Results: Importantly, this micro-emulsified eardrop demonstrated significantly greater in vitro antifungal activity than 3% boric acid and 2% acetic acid eardrops in twelve clinical fungal isolates from Vietnamese swimmers, especially on Curvularia, Cunninghamella, Aspergillus terreus, and Bipolaris. Although less pronounced than 1% clotrimazole, the finalized formulation demonstrates better antifungal kinetics and a broader activity spectrum. Conclusions: This work provides relevant experimental evidence on the use of Ocimum gratissimum essential oil in a microemulsion delivery system and demonstrates its efficacy against clinically relevant otomycosis pathogens. The results establish a foundation for future in vivo and clinical studies. Full article
(This article belongs to the Special Issue Nanoemulsions for Pharmaceutical and Biomedical Applications)
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2 pages, 145 KB  
Abstract
Nanoparticle-Based Encapsulation of Anaesthetics in Fish Anaesthesia: Advances and Perspectives
by Patrícia Carneiro, Cláudia A. Rocha, Sandra M. Monteiro, Carlos Venâncio and Luís M. Félix
Proceedings 2026, 146(1), 118; https://doi.org/10.3390/proceedings2026146118 - 17 Jun 2026
Viewed by 23
Abstract
Fish are continuously exposed to stress factors throughout their life cycle, making the use of anaesthetics essential for a wide range of experimental procedures. Currently, the most commonly used and FDA approved anaesthetic for fish research is Tricaine Methanesulfonate (MS-222). However, its use [...] Read more.
Fish are continuously exposed to stress factors throughout their life cycle, making the use of anaesthetics essential for a wide range of experimental procedures. Currently, the most commonly used and FDA approved anaesthetic for fish research is Tricaine Methanesulfonate (MS-222). However, its use has been associated with several undesirable effects, including hypoxemia, hypercapnia and hypoglycaemia, as well as environmental concerns due to its release through aquaculture effluents. These limitations highlight the need for alternative anaesthetic strategies. Natural compounds such as clove oil, menthol and thymol have been investigated as potential alternatives, demonstrating effective anaesthetic properties. However, their low aqueous solubility, represents a significant challenge, which may be overcome through nanoencapsulation. This approach can enhance solubility, enable controlled release, and reduce the effective dose required. Accordingly, the present study aims to provide an overview of the recent advances in nanoparticle-based encapsulation strategies for anaesthetic delivery in fish, with a focus on their efficacy, safety and environmental impact. Some studies have demonstrated the benefits of nanoencapsulation. In adult zebrafish (Danio rerio), lower concentrations of benzocaine were required when encapsulated in chitosan-PLGA nanoparticles, while lidocaine-loaded lipid NPs reduced bradycardia. In Nile Tilapia (Oreochromis niloticus), clove oil encapsulated in lipid-based nanocapsules enabled effective anaesthesia and prolonged release of the active compound eugenol. Similarly, mucoadhesive zein NPs, reduced the effective concentration of Eugenol by up to 50%. Monoterpenes such as menthol and thymol also show promise for zebrafish anaesthesia, demonstrating efficacy at 50 mg/L. These findings suggest that nanoparticle-based delivery systems can improve the efficacy and safety of fish anaesthetics while reducing required doses and potential environmental impact. Future research should focus on optimizing nanoparticle-anaesthetic systems by combining natural compounds with biocompatible and biodegradable nanocarriers (e.g., zein, chitosan or PLGA) to achieve controlled release, targeted delivery and minimization of side effects. Full article
(This article belongs to the Proceedings of The XI Iberian Congress of Ichthyology)
30 pages, 1059 KB  
Article
Integrating TRIZ, QFD, and Evolutionary Analysis for Eco Innovation: Redesigning a Laundry Detergent to Resolve Environmental Contradictions
by Andrés Morán-Durán, Guillermo Cortés-Robles, Omar Juárez-Rivera, Mónica Karina González-Rosas, Jesús Delgado-Maciel and José Roberto Grande-Ramírez
Appl. Syst. Innov. 2026, 9(6), 129; https://doi.org/10.3390/asi9060129 - 16 Jun 2026
Viewed by 346
Abstract
The growing environmental crisis, particularly water pollution from detergents, necessitates a shift from reactive compliance to proactive eco-innovation, as current methods often fail to systematically resolve trade-offs between performance, safety, and ecology. This study develops and illustrates the application of the Evolutionary-Driven Design [...] Read more.
The growing environmental crisis, particularly water pollution from detergents, necessitates a shift from reactive compliance to proactive eco-innovation, as current methods often fail to systematically resolve trade-offs between performance, safety, and ecology. This study develops and illustrates the application of the Evolutionary-Driven Design Framework (EDDF), an integrated methodology that combines PESTEL analysis, historical evolutionary pattern analysis, Quality Function Deployment (QFD) with a novel contradiction index, Theory of Inventive Problem Solving (TRIZ), and environmental assessment. The framework was applied to redesign a conventional laundry detergent with the objectives of zero phosphates, superior biodegradability (>85%), maintained efficacy, and controlled cost. The quantitative contradiction index matrix prioritized critical unsustainable parameters (e.g., EDTA, Cocamide DEA) for substitution over mere optimization. Through an iterative feedback loop, the process evolved from a biobased concentrate to an “enzymatic power tablet” (Concept B). This waterless, solid formulation uses sodium citrate as a biodegradable builder and an encapsulated multi-enzyme system, achieving an estimated >90% biodegradability and zero phosphates while meeting technical and economic targets. The EDDF provides a structured, anticipatory roadmap that transforms regulatory and market pressures into drivers of innovation, offering companies a promising method for designing sustainable products by proactively resolving contradictions and avoiding historical mistakes. Full article
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23 pages, 1492 KB  
Article
Encapsulation of Verbascum sinaiticum Leaf Extract as a Natural Antimicrobial for Controlling Microbial Growth in Beef During Refrigerated Storage
by Alemu Belay Legesse, Shimelis Admassu Emire, Timilehin Martins Oyinloye and Won Byong Yoon
Molecules 2026, 31(12), 2063; https://doi.org/10.3390/molecules31122063 - 12 Jun 2026
Viewed by 287
Abstract
The efficacy of plant-derived antimicrobials in meat systems is frequently limited by interactions with proteins, lipids, and other food matrix components that reduce the bioavailability and antimicrobial activity of phytochemicals. This study evaluated the antimicrobial effectiveness of Verbascum sinaiticum (V. sinaiticum) [...] Read more.
The efficacy of plant-derived antimicrobials in meat systems is frequently limited by interactions with proteins, lipids, and other food matrix components that reduce the bioavailability and antimicrobial activity of phytochemicals. This study evaluated the antimicrobial effectiveness of Verbascum sinaiticum (V. sinaiticum) leaf extract encapsulated using maltodextrin (MD), gum arabic (GA), and a maltodextrin–gum arabic blend (MDGA, 8:2 w/w) through freeze-drying for application in raw beef during refrigerated storage (4 °C). The encapsulation systems exhibited process yields of 42.5–54.7%, encapsulation efficiencies of 78.3–92.5%, and loading capacities of 18.5–24.3 mg GAE/g DW, with MDGA showing the highest encapsulation efficiency. The effects of encapsulation on microbial inhibition, physicochemical properties, and sensory quality were investigated over 15 days of storage. Aerobic plate counts in the control increased from 3.04 to 8.26 log CFU/g, whereas encapsulated treatments showed significantly lower final counts (p < 0.05), reaching 7.89 log CFU/g (MD), 7.96 log CFU/g (MDGA), and 7.95 log CFU/g (GA). Similarly, encapsulated treatments reduced Escherichia coli counts during storage, with maltodextrin (MD) exhibiting the greatest inhibitory effect (6.23 × 105 CFU/g) compared with the control (6.93 × 105 CFU/g) on day 15. However, reductions in Staphylococcus aureus, E. coli, Candida albicans, and Bacillus cereus remained below 1 log CFU/g, indicating limited antimicrobial efficacy under the tested conditions. All encapsulated treatments slowed pH increases during storage (6.20–6.34) relative to the control (6.62) on day 15 and preserved aroma quality throughout the storage period. Overall, encapsulation improved the antimicrobial performance of V. sinaiticum extract compared with the free extract, particularly in MD-based systems; however, the antimicrobial effects in beef remained modest. These findings highlight both the potential and current limitations of encapsulated plant-derived antimicrobials for meat preservation and emphasize the need for optimized delivery systems to enhance efficacy in complex food matrices. Full article
(This article belongs to the Special Issue Phenolic Compounds: Chemistry and Health Benefits)
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33 pages, 8473 KB  
Review
Innovative Approaches for Enhancing the Stability and Functionality of Essential Oils in Food Systems: A Critical and Bibliometric Review
by Neliswa H. Gcabashe, Yardjouma Silue and Olaniyi A. Fawole
Plants 2026, 15(12), 1811; https://doi.org/10.3390/plants15121811 - 12 Jun 2026
Viewed by 436
Abstract
Essential oils (EOs) are widely studied as natural antimicrobial and antioxidant agents in food systems. However, their high volatility, low water solubility, instability, phytotoxicity, and strong aroma often limit their consistent applicability for food preservation. This review critically examines the literature and synthesizes [...] Read more.
Essential oils (EOs) are widely studied as natural antimicrobial and antioxidant agents in food systems. However, their high volatility, low water solubility, instability, phytotoxicity, and strong aroma often limit their consistent applicability for food preservation. This review critically examines the literature and synthesizes current essential oil stabilization and delivery strategies in food systems, integrated with a bibliometric analysis of Scopus-indexed literature published before June 2025. The bibliometric findings showed an expanding research field, supported by 543 authors and 54 journals, revealing the disciplinary diversity of research on essential oil-based preservation systems. In addition, the review highlights a significant focus of studies on nanoemulsions, encapsulation, and active packaging in essential oil applications. Interestingly, the study also reveals the emergence of non-contact, or vapor-phase, technologies with improved release management. Furthermore, the review shows that essential oils’ functionality depends not only on major bioactive compounds but also on chemical class, oxidative sensitivity, release behavior, interactions with the food matrix, and the delivery platform. Mechanistically, stabilization technologies such as emulsions, encapsulation, and coatings/films can improve the protection, dispersion, and release of essential oils; however, their effectiveness strongly relies on formulation variables, matrix composition, and the regulatory framework. Emerging platforms such as nanofibers, zeolites, and metal–organic frameworks offer promising routes for vapor-phase or non-contact delivery systems, ensuring improved release control, functionality, and sensory quality, but may be limited by their scalability and production cost. However, a major research gap identified by this review is the imbalance between extensive “in vitro” studies and limited studies on real food matrices, which impedes understanding of the impacts of food matrices and packaging materials on essential oil release kinetics, antimicrobial efficacy, and sensory quality. Therefore, future research should integrate real-food applications, consumer acceptability, shelf-life performance, release-kinetic modeling, and techno-economic analysis to advance essential-oil-based technologies in food systems. Full article
(This article belongs to the Special Issue Plant-Derived Bioactive Compound Research)
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20 pages, 3089 KB  
Article
Chitosan–PLGA Hybrid Nanocarriers Enhance Therapeutic Delivery of Doxorubicin for Hepatocellular Carcinoma
by Shajahan Azeez, Anbazhagan Sathiyaseelan, Mohana Thiruchenduran, Kaviyarasan Venkatesan and Latha Ragunathan
Macromol 2026, 6(2), 42; https://doi.org/10.3390/macromol6020042 - 10 Jun 2026
Viewed by 270
Abstract
Hepatocellular carcinoma (HCC) is among the most prevalent and lethal malignancies worldwide, with limited therapeutic outcomes due to systemic toxicity and suboptimal efficacy of conventional chemotherapeutics such as doxorubicin (DOX). In this study, we formulated and standardized DOX-loaded chitosan/poly (lactic-co-glycolic acid) nanoparticles (DLCNs) [...] Read more.
Hepatocellular carcinoma (HCC) is among the most prevalent and lethal malignancies worldwide, with limited therapeutic outcomes due to systemic toxicity and suboptimal efficacy of conventional chemotherapeutics such as doxorubicin (DOX). In this study, we formulated and standardized DOX-loaded chitosan/poly (lactic-co-glycolic acid) nanoparticles (DLCNs) via a nanoprecipitation method and evaluated their therapeutic potential in a diethylnitrosamine (DEN)-induced Wistar rat model of HCC. Physicochemical analyses confirmed nanoscale size, favorable zeta potential, and high encapsulation efficiency, while Fourier-transform infrared spectroscopy (FTIR) verified polymer–drug interactions. Biochemical analysis revealed that DLCNs significantly normalized elevated liver function markers (Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), restored serum α-fetoprotein (AFP) to near-control levels, and reduced lipid peroxidation compared with free DOX and DEN controls. Antioxidant profiling demonstrated marked recovery of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), indicating restoration of hepatic redox balance. Histopathological evaluation further corroborated these findings, showing recovery of hepatic lobular architecture and reduction in necrosis and inflammatory infiltrates in DLCN-treated Wistar Albino rats, while free DOX groups exhibited hepatocellular damage. Overall, the results demonstrate that encapsulating DOX in a chitosan/PLGA nanocarrier improves therapeutic efficacy, mitigates hepatotoxicity, and enhances antioxidant defense, establishing DLCNs as a favorable candidate for HCC. Full article
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21 pages, 1134 KB  
Article
An Innovative Dendrimer-Based Retinol Delivery System for Xerosis Care: Stability, Tolerance, and Sustained Hydration
by Hafid Belhadj-Tahar and Lamri Naidja
J. Clin. Med. 2026, 15(12), 4435; https://doi.org/10.3390/jcm15124435 - 8 Jun 2026
Viewed by 151
Abstract
Background: Retinol is a mainstay of dermatological care due to its central role in epidermal differentiation, skin barrier repair, and tissue regeneration. However, its clinical use is limited by poor physicochemical stability, rapid photodegradation, and frequent skin intolerance, particularly in individuals with impaired [...] Read more.
Background: Retinol is a mainstay of dermatological care due to its central role in epidermal differentiation, skin barrier repair, and tissue regeneration. However, its clinical use is limited by poor physicochemical stability, rapid photodegradation, and frequent skin intolerance, particularly in individuals with impaired skin barrier function. Supramolecular biovectorization strategies could overcome these limitations. Objectives: This study aimed to evaluate the impact of third-generation dendritic poly-L-lysine (PLL_G3; 22 kDa, ~7 nm) on retinol stability, skin tolerance, and skin functional performance. Methods: A supramolecular retinol-poly-L-lysine complex was characterized in terms of encapsulation efficiency and physicochemical stability using HPLC and UV spectroscopy under oxidative, thermal, and photochemical stress. The stability of the formulation was evaluated as hydrophilic emulsion over a three-month period. Skin functional efficacy was evaluated by corneometric analysis of stratum corneum hydration after topical application, as well as by clinical assessment of tolerance and efficacy after repeated daily use over 28 days in subjects presenting xerosis, defined as dry to very dry skin. Results: Retinol remained structurally intact in the PLL_G3 matrix, confirming a reversible, non-covalent encapsulation mechanism. The formulation exhibited high physicochemical stability, with only minimal changes after prolonged UV exposure. Corneometric measurements showed a rapid and sustained increase in skin hydration, reaching +61.5% two hours after application. After 28 days of repeated use, the formulation was well tolerated, with no signs of irritation or sensitization, and demonstrated significant improvements in skin dryness, suppleness, and comfort. Conclusions: PLL_G3-based supramolecular vectorization significantly improves stability, tolerance, and functional hydration of the skin by retinol. By enabling controlled release while preserving the integrity of the epidermal barrier, poly-L-lysine dendrimers represent a clinically relevant strategy for safer and more effective topical use of retinol, particularly on sensitive, xerotic, inflammatory, and photoaged skin. Full article
(This article belongs to the Special Issue Emerging Therapies: Clinical Trials and Insights in Psoriasis)
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22 pages, 1876 KB  
Article
Development of Slow-Release Salt Storage Fillers and Performance Evaluation of Salt-Storage Pavement
by Yanhai Yang, Dongning Ban, Ye Yang and Guanliang Chen
Materials 2026, 19(12), 2450; https://doi.org/10.3390/ma19122450 - 8 Jun 2026
Viewed by 224
Abstract
To address the issues of poor sustained-release behavior and limited long-term efficacy associated with conventional salt-storage materials, this study developed the epoxy-resin-encapsulated slow-release salt-storage filler to enhance both the engineering performance and the deicing/snow-melting capacity of salt-storage pavements. In this study, attapulgite was [...] Read more.
To address the issues of poor sustained-release behavior and limited long-term efficacy associated with conventional salt-storage materials, this study developed the epoxy-resin-encapsulated slow-release salt-storage filler to enhance both the engineering performance and the deicing/snow-melting capacity of salt-storage pavements. In this study, attapulgite was optimized and selected as the salt storage carrier through the adoption of pesticide coating technology and experimental testing, wherein a deicing salt blend with a CaCl2 to NaCl mass ratio of 2:1 was loaded via a wet adsorption method. Subsequently, using dimethicone as the surface modifier, the optimal encapsulation process was determined to involve the dilution ratio of epoxy resin to cyclohexanone of 4:1 and the curing agent dosage of 30% by weight. The results indicated that the recommended content of the filler should not exceed 5%. The filler reduced the high-temperature stability and water stability of the mixture, while the low-temperature crack resistance first increased and then decreased, peaking at the 2% filler content with an improvement of 12.2%. The water stability was the most significantly affected by the filler content. Ice–snow melting performance tests demonstrated that the salt-storage mixture with 5% filler achieved the deicing rate of 56.35% at −5 °C, meeting the industry standard requirements. The self-prepared slow-release salt-storage filler exhibited superior long-term ice–snow melting performance to V-260, with the slow-release duration extended by 60%. The salt release process was divided into three distinct stages: rapid dissolution, stable release and slow dissolution. The 60 °C was determined as the optimal temperature for the accelerated immersion testing, which the accelerated test could effectively simulate the natural immersion process. Based on the prediction model established accordingly, the functional service life of snow-melting for this slow-release salt-storage asphalt pavement in northern area was estimated be approximately 4.07 years. The slow-release salt-storage filler fabricated in this work possesses both remarkable sustained-release behavior and deicing efficacy. The findings provide the technical foundation for the development of novel salt-storage pavement materials, performance characterization, and mechanistic analysis of snow-ice melting. Full article
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