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Search Results (780)

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Keywords = particle size polydispersity

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15 pages, 2347 KB  
Article
Valorization of Cavia porcellus By-Products via Ultrasound-Assisted Collagen Extraction: Optimization and Characterization
by Gussieff Lino Santos, Milady Esteban Valenzuela, Greta Hinostroza-Quiñonez, Omar Flores Ramos, Edgar Acosta López, Rodolfo Tello Saavedra, Edgar Rojas Zacarias, Humberto Bonilla, Ever Ingaruca Álvarez and Clara Espinoza Silva
Foods 2025, 14(20), 3542; https://doi.org/10.3390/foods14203542 - 17 Oct 2025
Viewed by 110
Abstract
The by-products of Cavia porcellus (legs and head) were valorized for collagen extraction using ultrasound-assisted extraction (UAE). Process optimization was performed through response surface methodology (central composite design) considering amplitude, cycle, and time as factors. Samples were pretreated with NaOH and butyl alcohol, [...] Read more.
The by-products of Cavia porcellus (legs and head) were valorized for collagen extraction using ultrasound-assisted extraction (UAE). Process optimization was performed through response surface methodology (central composite design) considering amplitude, cycle, and time as factors. Samples were pretreated with NaOH and butyl alcohol, followed by acetic acid extraction under controlled sonication. The quadratic models for yield and hydroxyproline showed excellent fit (high R2, R2adj, and R2pred) with no significant lack of fit. The optimal conditions were identified at 100% amplitude, cycle = 1, and 27.47 min, and these were validated experimentally, yielding 28.15 ± 0.19% collagen and 4.18 ± 0.12% hydroxyproline, values that closely matched predictions. The optimal extract exhibited a hydrodynamic diameter of 599.3 nm, a ζ-potential of −61.3 mV, and a polydispersity index of 0.33, indicating a highly stable colloidal dispersion with submicron fibrils. SEM micrographs confirmed fibrillar bundles consistent with the particle size distribution, while FTIR spectra showed characteristic amide bands indicative of triple-helix preservation. These results demonstrate that UAE of guinea pig by-products produces collagen with high structural integrity and colloidal stability, highlighting its potential for food and biomaterial applications. Full article
19 pages, 1457 KB  
Article
Development and Evaluation of Hyaluronic Acid-Chitosan Coated Liposomes for Enhanced Delivery of Resveratrol to Breast Cancer Cells
by Yin Yin Myat, Khin Khin Gyi, Pornthida Riangjanapatee, Chuda Chittasupho, Songyot Anuchapreeda and Siriporn Okonogi
Polysaccharides 2025, 6(4), 93; https://doi.org/10.3390/polysaccharides6040093 - 10 Oct 2025
Viewed by 376
Abstract
Resveratrol (RES), a naturally occurring polyphenolic compound with well-documented anticancer potential, is limited in clinical application due to its poor aqueous solubility and low bioavailability. This study aimed to develop RES-loaded liposomes coated sequentially with chitosan (CS) and hyaluronic acid-chitosan (HA) (RES-HA-CS-Lip) to [...] Read more.
Resveratrol (RES), a naturally occurring polyphenolic compound with well-documented anticancer potential, is limited in clinical application due to its poor aqueous solubility and low bioavailability. This study aimed to develop RES-loaded liposomes coated sequentially with chitosan (CS) and hyaluronic acid-chitosan (HA) (RES-HA-CS-Lip) to enhance RES stability, delivery, and anticancer efficacy in breast cancer cells. HA-CS-coated liposomes were prepared using a thin-film hydration technique. Their physicochemical characteristics were thoroughly investigated through dynamic light scattering, transmission electron microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. The optimized RES-HA-CS-Lip exhibited spherical morphology with an average particle size of 212 nm, a narrow polydispersity index (<0.4), a zeta potential of +9.04 ± 1.0 mV, and high entrapment efficiency of 82.16%. Stability studies demonstrated superior retention of size, surface charge, and encapsulation efficiency over 28 days at both 4 °C and 25 °C. In vitro release profiles at physiological and acidic pH revealed sustained drug release, with enhanced release under acidic conditions mimicking the tumor microenvironment. Antioxidant activity, assessed via DPPH and ABTS radical-scavenging assays, indicated that RES retained its radical-scavenging potential upon encapsulation. Cytotoxicity assays demonstrated markedly improved anticancer activity against MCF-7 breast cancer cells, with an IC50 of 13.08 μg/mL at 48 h, while maintaining high biocompatibility toward normal HaCaT keratinocytes. RES-HA-CS-Lip demonstrated excellent stability against degradation and aggregation. Overall, these findings highlight HA-CS-coated liposomes as a promising polysaccharide-based nanocarrier that enhances stability, bioactivity, and therapeutic efficacy of RES, representing a potential strategy for targeted breast cancer therapy. Full article
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14 pages, 2579 KB  
Article
Targeted Delivery of VEGF-siRNA to Glioblastoma Using Orientation-Controlled Anti-PD-L1 Antibody-Modified Lipid Nanoparticles
by Ayaka Matsuo-Tani, Makoto Matsumoto, Takeshi Hiu, Mariko Kamiya, Longjian Geng, Riku Takayama, Yusuke Ushiroda, Naoya Kato, Hikaru Nakamura, Michiharu Yoshida, Hidefumi Mukai, Takayuki Matsuo and Shigeru Kawakami
Pharmaceutics 2025, 17(10), 1298; https://doi.org/10.3390/pharmaceutics17101298 - 4 Oct 2025
Viewed by 692
Abstract
Background/Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor with limited therapeutic options despite multimodal treatment. Small interfering RNA (siRNA)-based therapeutics can silence tumor-promoting genes, but achieving efficient and tumor-specific delivery remains challenging. Lipid nanoparticles (LNPs) are promising siRNA carriers; however, conventional [...] Read more.
Background/Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor with limited therapeutic options despite multimodal treatment. Small interfering RNA (siRNA)-based therapeutics can silence tumor-promoting genes, but achieving efficient and tumor-specific delivery remains challenging. Lipid nanoparticles (LNPs) are promising siRNA carriers; however, conventional antibody conjugation can impair antigen recognition and complicate manufacturing. This study aimed to establish a modular Fc-binding peptide (FcBP)-mediated post-insertion strategy to enable PD-L1-targeted delivery of VEGF-siRNA via LNPs for GBM therapy. Methods: Preformed VEGF-siRNA-loaded LNPs were functionalized with FcBP–lipid conjugates, enabling non-covalent anchoring of anti-PD-L1 antibodies through Fc interactions. Particle characteristics were analyzed using dynamic light scattering and encapsulation efficiency assays. Targeted cellular uptake and VEGF gene silencing were evaluated in PD-L1-positive GL261 glioma cells. Anti-tumor efficacy was assessed in a subcutaneous GL261 tumor model following repeated intratumoral administration using tumor volume and bioluminescence imaging as endpoints. Results: FcBP post-insertion preserved LNP particle size (125.2 ± 1.3 nm), polydispersity, zeta potential, and siRNA encapsulation efficiency. Anti-PD-L1–FcBP-LNPs significantly enhanced cellular uptake (by ~50-fold) and VEGF silencing in PD-L1-expressing GL261 cells compared to controls. In vivo, targeted LNPs reduced tumor volume by 65% and markedly suppressed bioluminescence signals without inducing weight loss. Final tumor weight was reduced by 63% in the anti-PD-L1–FcBP–LNP group (656.9 ± 125.4 mg) compared to the VEGF-siRNA LNP group (1794.1 ± 103.7 mg). The FcBP-modified LNPs maintained antibody orientation and binding activity, enabling rapid functionalization with targeting antibodies. Conclusions: The FcBP-mediated post-insertion strategy enables site-specific, modular antibody functionalization of LNPs without compromising physicochemical integrity or antibody recognition. PD-L1-targeted VEGF-siRNA delivery demonstrated potent, selective anti-tumor effects in GBM murine models. This platform offers a versatile approach for targeted nucleic acid therapeutics and holds translational potential for treating GBM. Full article
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21 pages, 2757 KB  
Article
Process Parameter Screening Through Fractional Factorial Design for the Synthesis of Gold Nanoparticles
by Harshilkumar Jani, Ketan Ranch, Vijay R. Chidrawar, Popat Mohite and Sudarshan Singh
Processes 2025, 13(10), 3157; https://doi.org/10.3390/pr13103157 - 2 Oct 2025
Viewed by 541
Abstract
Nanoparticles (NPs) of noble metals such as gold have garnered significant attention due to their novel optical and catalytic properties, their theranostic properties, as they are biocompatible, and they attract considerable interest in a range of applications including targeted drug delivery. In this [...] Read more.
Nanoparticles (NPs) of noble metals such as gold have garnered significant attention due to their novel optical and catalytic properties, their theranostic properties, as they are biocompatible, and they attract considerable interest in a range of applications including targeted drug delivery. In this study, a fractional factorial design (FFD) is applied to systematically investigate the influence of key synthesis parameters (independent variables) at a low level (−1) and a high level (+1), including the reducing agent type (chitosan or trisodium citrate), concentration of reducing agent (10 to 40 mg), pH (3.5 to 8.5), temperature (60 to 100 °C), agitation time (5 to 15 min), and agitation speed (400 to 1200 rpm), on the dependent parameters—particle size and polydispersity index of gold nanoparticles (GNPs). The goal of this study was to provide a comprehensive understanding of the interplay between these parameters and their interaction effect on the characteristics of gold nanoparticles. A fractional factorial design allowed for efficient screening of the parameter space while minimizing the number of experiments required. The results demonstrated that pH, reducing agent, reducing agent–concentration, reducing agent–concentration of reducing agent–pH, and reducing agent–temperature interactions played significant roles in determining the particle size of the synthesized GNPs. Moreover, pH and reducing agent–concentration were identified as the major factors influencing the dispersity of the NPs. This study sheds light on the complex relationships between synthesis parameters and NP characteristics, offering an insight into the capacity for optimizing the synthesis process in order to tailor the desired properties of GNPs. The findings contribute to the growing field of NP synthesis and advance the understanding of the underlying mechanisms governing the formation of GNPs with specific size and dispersity characteristics. Full article
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19 pages, 2144 KB  
Article
Nanoparticles Loaded with Lippia graveolens Essential Oil as a Topical Delivery System: In Vitro Antiherpetic Activity and Biophysical Parameters Evaluation
by Nancy Nallely Espinosa-Carranza, Rocío Álvarez-Román, David A. Silva-Mares, Luis A. Pérez-López, Catalina Leos-Rivas, Catalina Rivas-Morales, Juan Gabriel Báez-González and Sergio Arturo Galindo-Rodríguez
Pharmaceutics 2025, 17(10), 1286; https://doi.org/10.3390/pharmaceutics17101286 - 2 Oct 2025
Viewed by 450
Abstract
Background/Objectives: The skin is a protective barrier against pathogens such as herpes simplex virus type 1 (HSV-1), which causes recurrent and highly prevalent skin infections worldwide. The increasing resistance of HSV-1 to conventional treatments has driven the search for new therapeutic alternatives. [...] Read more.
Background/Objectives: The skin is a protective barrier against pathogens such as herpes simplex virus type 1 (HSV-1), which causes recurrent and highly prevalent skin infections worldwide. The increasing resistance of HSV-1 to conventional treatments has driven the search for new therapeutic alternatives. In this context, the essential oil of Lippia graveolens (EOL) has demonstrated promising antiviral activity; however, its high volatility limits direct skin application. To overcome this, polymeric nanoparticles (NPs) loaded with EOL were developed to improve its availability and antiviral efficacy. Methods: Nanoformulations were prepared by nanoprecipitation, and their antiviral activity against HSV-1 was evaluated using the plaque reduction assay. The effect of the nanoformulations on skin barrier integrity was assessed using an ex vivo porcine skin model and non-invasive techniques. Results: The NP-EOL exhibited physicochemical properties favorable for skin deposition, including a particle size around 200 nm, a polydispersity index of ≤ 0.2, and negative zeta potential. Moreover, NP-EOL showed 1.85-fold higher antiviral activity against HSV-1 compared with free EOL, while also reducing cytotoxicity in Vero cells. Conclusions: Results demonstrated that the NPs promoted skin hydration without altering pH or transepidermal water loss, suggesting they do not disrupt skin homeostasis. This study supports the potential of NP-based systems as effective topical delivery vehicles for EOL, representing a promising therapeutic alternative against HSV-1 skin infections. Full article
(This article belongs to the Special Issue Novel Drug Delivery Systems for the Treatment of Skin Disorders)
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23 pages, 5279 KB  
Article
Green Synthesis of Zinc Oxide Nanoparticles: Physicochemical Characterization, Photocatalytic Performance, and Evaluation of Their Impact on Seed Germination Parameters in Crops
by Hanan F. Al-Harbi, Manal A. Awad, Khalid M. O. Ortashi, Latifah A. AL-Humaid, Abdullah A. Ibrahim and Asma A. Al-Huqail
Catalysts 2025, 15(10), 924; https://doi.org/10.3390/catal15100924 - 28 Sep 2025
Viewed by 775
Abstract
This study reports on green-synthesized zinc oxide nanoparticles (ZnONPs), focusing on their physicochemical characterization, photocatalytic properties, and agricultural applications. Dynamic light scattering (DLS) analysis revealed a mean hydrodynamic diameter of 337.3 nm and a polydispersity index (PDI) of 0.400, indicating moderate polydispersity and [...] Read more.
This study reports on green-synthesized zinc oxide nanoparticles (ZnONPs), focusing on their physicochemical characterization, photocatalytic properties, and agricultural applications. Dynamic light scattering (DLS) analysis revealed a mean hydrodynamic diameter of 337.3 nm and a polydispersity index (PDI) of 0.400, indicating moderate polydispersity and nanoparticle aggregation, typical of biologically synthesized systems. High-resolution transmission electron microscopy (HR-TEM) showed predominantly spherical particles with an average diameter of ~28 nm, exhibiting slight agglomeration. Energy-dispersive X-ray spectroscopy (EDX) confirmed the elemental composition of zinc and oxygen, while X-ray diffraction (XRD) analysis identified a hexagonal wurtzite crystal structure with a dominant (002) plane and an average crystallite size of ~29 nm. Photoluminescence (PL) spectroscopy displayed a distinct near-band-edge emission at ~462 nm and a broad blue–green emission band (430–600 nm) with relatively low intensity. The ultraviolet–visible spectroscopy (UV–Vis) absorption spectrum of the synthesized ZnONPs exhibited a strong absorption peak at 372 nm, and the optical band gap was calculated as 2.67 eV using the Tauc method. Fourier-transform infrared spectroscopy (FTIR) analysis revealed both similarities and distinct differences to the pigeon extract, confirming the successful formation of nanoparticles. A prominent absorption band observed at 455 cm−1 was assigned to Zn–O stretching vibrations. X-ray photoelectron spectroscopy (XPS) analysis showed that raw pigeon droppings contained no Zn signals, while their extract provided organic biomolecules for reduction and stabilization, and it confirmed Zn2+ species and Zn–O bonding in the synthesized ZnONPs. Photocatalytic degradation assays demonstrated the efficient removal of pollutants from sewage water, leading to significant reductions in total dissolved solids (TDS), chemical oxygen demand (COD), and total suspended solids (TSS). These results are consistent with reported values for ZnO-based photocatalytic systems, which achieve biochemical oxygen demand (BOD) levels below 2 mg/L and COD values around 11.8 mg/L. Subsequent reuse of treated water for irrigation yielded promising agronomic outcomes. Wheat and barley seeds exhibited 100% germination rates with ZnO NP-treated water, which were markedly higher than those obtained using chlorine-treated effluent (65–68%) and even the control (89–91%). After 21 days, root and shoot lengths under ZnO NP irrigation exceeded those of the control group by 30–50%, indicating enhanced seedling vigor. These findings demonstrate that biosynthesized ZnONPs represent a sustainable and multifunctional solution for wastewater remediation and agricultural enhancement, positioning them as a promising candidate for integration into green technologies that support sustainable urban development. Full article
(This article belongs to the Section Photocatalysis)
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24 pages, 5557 KB  
Article
The Antidepressant Effect of Targeted Release of Ketamine-Loaded Nanodroplets Stimulated by Low-Intensity Focused Ultrasound
by Bailing Wu, Yu Xu, Yuhang Xie, Youzhuo Li, Yue Huang, Yuran Feng and Mei Zhu
Pharmaceutics 2025, 17(10), 1251; https://doi.org/10.3390/pharmaceutics17101251 - 24 Sep 2025
Viewed by 358
Abstract
Objectives: Ketamine has demonstrated rapid and sustained antidepressant effects; however, its clinical utility is limited by the risk of addiction and systemic side effects. This study aimed to develop ketamine-loaded nanodroplets (Ket-NDs) with high encapsulation efficiency (EE) and stability for targeted low-dose [...] Read more.
Objectives: Ketamine has demonstrated rapid and sustained antidepressant effects; however, its clinical utility is limited by the risk of addiction and systemic side effects. This study aimed to develop ketamine-loaded nanodroplets (Ket-NDs) with high encapsulation efficiency (EE) and stability for targeted low-dose intravenous (IV) administration in a mice model of depression. Low-intensity focused ultrasound (LIFU) was employed to induce transcranial, region-specific drug release in the lateral habenula (LHb). Methods: Ket-NDs were synthesized using a thin-film hydration method with sonication and emulsification, incorporating perfluoropentane as the core material. Characterization was performed using light microscopy, cryogenic scanning electron microscopy (cryo-SEM), transmission electron microscopy, and dynamic light scattering (DLS). Drug EE and loading efficiency (LE) were quantified by reversed-phase high-performance liquid chromatography. A chronic restraint stress model was established, and Ket-NDs were administered intravenously followed by LIFU targeting the LHb. Antidepressant efficacy and biosafety were systematically evaluated. Results: (1) Ket-NDs exhibited uniform spherical morphology and a narrow size distribution, as confirmed by DLS (particle size: 139.75 ± 9.43 nm; Polydispersity index: 0.225 ± 0.025) and cryo-SEM analysis (number-average diameter: 109.5 ± 10.4 nm). The zeta potential was −15.93 ± 5.906 mV, and the formulation remained stable under 4 °C storage. (2) Ket-NDs demonstrated high EE (78.25 ± 16.13%) and LE (15.55 ± 4.49%). (3) In depressive mice, IV administration of Ket-NDs followed by LIFU targeting the LHb significantly improved behavioral outcomes: increased locomotor activity in the open field test, elevated sucrose preference index, and reduced immobility time in the tail suspension test. (4) Safety assessments revealed no significant organ toxicity or brain tissue damage in ultrasound-exposed regions. Conclusions: In summary, this study developed stable Ket-NDs. When combined with LIFU, they enable precise regional drug delivery to the brain, showcasing a promising treatment strategy for depression with reduced systemic side effects. Full article
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23 pages, 10763 KB  
Article
Enhanced Efinaconazole Permeation and Activity Against Trichophyton rubrum and Trichophyton mentagrophytes with a Self-Nanoemulsifying Drug Delivery System
by Seo Wan Yun, Jeong Gyun Lee, Chul Ho Kim and Kyeong Soo Kim
Pharmaceutics 2025, 17(9), 1230; https://doi.org/10.3390/pharmaceutics17091230 - 22 Sep 2025
Viewed by 511
Abstract
Background: Onychomycosis responds poorly to topical therapy, and efinaconazole (EFN) has low aqueous solubility. Methods: This study aimed to develop a 10% w/w EFN self-nanoemulsifying system (SNEDDS) with improved solubility, permeation, antifungal activity, and stability. Excipients were screened by [...] Read more.
Background: Onychomycosis responds poorly to topical therapy, and efinaconazole (EFN) has low aqueous solubility. Methods: This study aimed to develop a 10% w/w EFN self-nanoemulsifying system (SNEDDS) with improved solubility, permeation, antifungal activity, and stability. Excipients were screened by EFN saturation solubility. An MCT oil/Solutol HS 15/Labrafil M2125 CS SNEDDS (5/75/20, w/w) was optimized via a pseudo-ternary diagram. Characterization included droplet size, PDI, and zeta potential, morphology, and drug–excipient compatibility. Solubility was measured across pH. Permeation of EFN SNEDDS vs. EFN suspension was tested by Franz diffusion cells. Antifungal activity against Trichophyton rubrum and Trichophyton mentagrophytes was assessed by paper-disc diffusion, and hyphal damage on human nails was examined by SEM. Stability was studied for six months under room, accelerated, and stress conditions. Results: The optimized SNEDDS formed sub-50 nm droplets with low polydispersity and favourable zeta potential. Solubility was maintained across pH, and cumulative permeation increased 13.6-fold versus suspension. Paper-disc assays showed larger inhibition zones at lower EFN doses. SEM on human nails revealed marked hyphal destruction. TEM confirmed spherical nanoemulsion droplets. FT-IR showed no new peaks, supporting compatibility. Particle size, PDI, zeta potential, and drug content remained stable over six months under all storage conditions. Conclusions: A 10% w/w EFN SNEDDS enhanced solubility, transungual permeation, and antifungal efficacy while maintaining robust stability, supporting its potential as an ethanol-free therapy for onychomycosis. Full article
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16 pages, 3270 KB  
Article
Albumin/Hyaluronic Acid Gel Nanoparticles Loaded with a Pyrimidine-Based Drug for Potent Anticancer Activity
by Sofia Teixeira, Débora Ferreira, Ligia R. Rodrigues, M. Alice Carvalho and Elisabete M. S. Castanheira
Gels 2025, 11(9), 759; https://doi.org/10.3390/gels11090759 - 21 Sep 2025
Viewed by 530
Abstract
A pyrimidine-based compound (PP) was recently found to be a promising anticancer agent for colorectal and breast cancers. However, this compound exhibited low selectivity and poor water solubility. To address these challenges, albumin gel nanoparticles were used, where the gel matrix [...] Read more.
A pyrimidine-based compound (PP) was recently found to be a promising anticancer agent for colorectal and breast cancers. However, this compound exhibited low selectivity and poor water solubility. To address these challenges, albumin gel nanoparticles were used, where the gel matrix is formed by cross-linking of BSA molecules, allowing for a high concentration of this hydrophobic drug to be carried with no cytotoxicity to non-tumor cells. Functionalization with hyaluronic acid (HA) was employed to target CD44-overexpressing cancer cells, specifically triple-negative breast cancer (MDA-MB-231) and colorectal cancer cell lines (HCT 116). The gel nanoparticles present mean sizes below 250 nm, very low polydispersity, small aggregation tendency, and excellent colloidal stability in PBS buffer for a storage period of 30 days. Moreover, the drug-loaded particles showed high encapsulation efficiencies (above 85%) and sustained release profiles. Drug-loaded BSA/HA particles (PP-HA-BSA-NPs) revealed advantageous activity, presenting around 55% and 23% cell viability at a IC50 drug concentration for triple-negative breast cancer (the most aggressive breast cancer subtype) and colorectal cancer (second leading cause of cancer-related deaths), respectively. In conclusion, these nanoparticles outperform the ones without HA, demonstrating target capabilities, while retaining the drug’s anticancer activity and reducing the drug’s toxicity. These results are promising for future in vivo assays and clinical translational applications. Full article
(This article belongs to the Special Issue Advanced Hydrogels for Controlled Drug Delivery (2nd Edition))
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25 pages, 3468 KB  
Article
Baicalin–Myricetin-Coated Selenium Nanoparticles Mitigate Pathology in an Aβ1-42 Mice Model of Alzheimer’s Disease
by Rosa Martha Pérez Gutiérrez, Julio Téllez Gómez, José María Mota Flores, Mónica Corea Téllez and Alethia Muñiz Ramírez
Pharmaceuticals 2025, 18(9), 1391; https://doi.org/10.3390/ph18091391 - 17 Sep 2025
Viewed by 494
Abstract
Background: Current Alzheimer’s disease (AD) treatments primarily focus on symptom management and offer limited potential to arrest disease progression. To address this limitation, we developed baicalin–myricetin (BM) functionalized selenium nanoparticles (SeNPs), termed BMSe@BSA, aimed at multi-targeted neuroprotection. Materials and Methods: BMSe@BSA [...] Read more.
Background: Current Alzheimer’s disease (AD) treatments primarily focus on symptom management and offer limited potential to arrest disease progression. To address this limitation, we developed baicalin–myricetin (BM) functionalized selenium nanoparticles (SeNPs), termed BMSe@BSA, aimed at multi-targeted neuroprotection. Materials and Methods: BMSe@BSA nanoparticles were synthesized via a gel–sol technique using bovine serum albumin (BSA), ascorbic acid, selenous acid, and BM. Interactions among BSA, BM, and SeNPs were characterized by microscopy and spectrometry. Cytotoxicity was assessed on RAW 264.7 and PC12 cells to determine biocompatibility. Neuroinflammation and cognitive function were evaluated in C57BL6/J mice challenged with Aβ1-42. Recognition memory was tested through open-field exploration, novel object recognition (NOR), and T-maze assays. Inflammatory markers (IL-1β and TNF-α) and microglial changes in the cerebral cortex were quantified, while amyloid fibril morphology was assessed using atomic force microscopy (AFM). Results: Spectroscopic analysis verified successful BM functionalization. Transmission electron microscopy revealed a spherical morphology with an average particle size of 90.57 nm, zeta potential of 27.2 mV, and a polydispersity index (PDI) of 0.270. BM entrapment efficiency reached approximately 90%. Cytotoxicity assays confirmed the nanoparticles’ safety, with no toxicity observed at concentrations up to 400 µg/mL after 4 h of incubation. BMSe@BSA effectively inhibited amyloid fibril formation, downregulated pro-inflammatory cytokine expression, preserved neuronal integrity, and significantly enhanced cognitive performance in AD mouse models. Conclusion: BMSe@BSA appear as a potential nanotherapeutic approach for targeted brain delivery and multi-pathway intervention in Alzheimer’s disease. Full article
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36 pages, 4364 KB  
Article
Improving Alzheimer’s Disease and Parkinson’s Disease in Rats with Nanoemulsion and Byproducts Prepared from Cinnamon Leaves
by Bing-Huei Chen, Chen-Te Jen, Chia-Chuan Wang and Min-Hsiung Pan
Pharmaceutics 2025, 17(9), 1200; https://doi.org/10.3390/pharmaceutics17091200 - 15 Sep 2025
Viewed by 620
Abstract
Background/Objectives: Cinnamon leaves, an important source of the functional compound cinnamaldehyde (CA), have been shown to be effective in improving type II diabetes and Parkinson’s disease (PD) in rats following the incorporation of cinnamon leaf extract into a nanoemulsion. However, the effect [...] Read more.
Background/Objectives: Cinnamon leaves, an important source of the functional compound cinnamaldehyde (CA), have been shown to be effective in improving type II diabetes and Parkinson’s disease (PD) in rats following the incorporation of cinnamon leaf extract into a nanoemulsion. However, the effect of a cinnamon leaf extract nanoemulsion (CLEN) on improving Alzheimer’s disease (AD), the most prevalent type of dementia, remains unexplored. The objectives of this study were to determine functional compounds in cinnamon leaves by UPLC-MS/MS, followed by the preparation of a nanoemulsion and its byproducts to study their effects on AD and PD in rats. Methods: Oven-dried (60 °C for 2 h) cinnamon leaf powder and hydrosol, obtained by steam distillation of cinnamon leaf powder, were stored at 4 °C. After determination of basic composition (crude protein, crude fat, carbohydrate, moisture and ash) of cinnamon leaf powder, it was extracted with 80% ethanol with sonication at 60 °C for 2 h and analyzed for bioactive compounds by UPLC-MS/MS. Then, the CLEN was prepared by mixing cinnamon leaf extract rich in CA with lecithin, soybean oil, tween 80 and ethanol in an optimal ratio, followed by evaporation to form thin-film and redissolving in deionized water. For characterization, mean particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and surface morphology were determined. Animal experiments were done by dividing 90 male rats into 10 groups (n = 9), with groups 2–8 being subjected to mini-osmotic pump implantation surgery in brain to infuse Amyloid-beta 40 (Aβ40) solution in groups 2–8 for induction of AD, while groups 9 and 10 were pre-fed respectively with cinnamon powder in water (0.5 g/10 mL) and in hydrosol for 4 weeks, followed by induction of AD as shown above. Different treatments for a period of 4 weeks included groups 1–9, with group 1 (control) and group 2 feeding with sterilized water, while groups 3, 4 and 5 were fed respectively with high (90 mg/kg), medium (60 mg/kg) and low (30 mg/kg) doses of cinnamon leaf extracts, groups 6, 7 and 8 fed respectively with high (90 mg/kg), medium (60 mg/kg) and low (30 mg/kg) doses of nanoemulsions, groups 9 and 10 fed respectively with 10 mL/kg of cinnamon powder in water and hydrosol (0.5 g/10 mL). Morris water maze test was conducted to determine short-term memory, long-term memory and space probing of rats. After sacrificing of rats, brain and liver tissues were collected for determination of Aβ40, BACE1 and 8-oxodG in hippocampi, and AchE and malondialdehyde (MDA) in cortices, antioxidant enzymes (SOD, CAT, GSH-Px) and MDA in both cortices and livers, and dopamine in brain striata by using commercial kits. Results: The results showed that the highest level of CA (18,250.7 μg/g) was in the cinnamon leaf powder. The CLEN was prepared successfully, with an average particle size of 17.1 nm, a polydispersity index of 0.236, a zeta potential of −42.68 mV, and high stability over a 90-day storage period at 4 °C. The Morris water maze test revealed that the CLEN treatment was the most effective in improving short-term memory, long-term memory, and spatial probe test results in AD rats, followed by the cinnamon leaf extract (CLE), powder in hydrosol (PH), and powder in water (PW). Additionally, both CLEN and CLE treatments indicated a dose-dependent improvement in AD rats, while PH and PW were effective in preventing AD occurrence. Furthermore, AD occurrence accompanied by PD development was demonstrated in this study. With the exception of the induction group, declines in Aβ40, BACE1, and 8-oxodG in the hippocampi and AchE and MDA in the cortices of rats were observed for all the treatments, with the high-dose CLEN (90 mg/kg bw) exhibiting the highest efficiency. The antioxidant enzyme activity, including that of SOD, CAT, and GSH-Px, in the cortices of rats increased. In addition, dopamine content, a vital index of PD, was increased in the striata of rats, accompanied by elevations in SOD, CAT, and GSH-Px and decreased MDA in rat livers. Conclusions: These outcomes suggest that the CLEN possesses significant potential for formulation into a functional food or botanical drug for the prevention and treatment of AD and/or PD in the future. Full article
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19 pages, 1068 KB  
Article
Liposomal Encapsulation of Pine Green Cone Essential Oil: The Influence of the Carrier on the Enhancement of Anti-Inflammatory Activity
by Snježana Mirković, Vanja Tadić, Marina Tomović, Anica Petrović, Marijana Andjić, Jovana Bradić, Sanja Perać, Aleksandar Radojković, Jelena Jovanović and Ana Žugić
Pharmaceutics 2025, 17(9), 1182; https://doi.org/10.3390/pharmaceutics17091182 - 11 Sep 2025
Viewed by 604
Abstract
Background/Objectives: This study aimed to investigate the traditionally claimed anti-inflammatory effect of essential oil (EO) derived from pine green cones per se and after encapsulation into liposomes, which is expected to enhance its bioactivity and stability. Methods: The chemical profiling of EO [...] Read more.
Background/Objectives: This study aimed to investigate the traditionally claimed anti-inflammatory effect of essential oil (EO) derived from pine green cones per se and after encapsulation into liposomes, which is expected to enhance its bioactivity and stability. Methods: The chemical profiling of EO was conducted using GC/GC-MS. The physico-chemical characterization of the liposomal formulation (LEO) included encapsulation efficiency, FTIR spectroscopy, and AFM imaging. Additionally, parameters such as mean particle diameter, polydispersity index, zeta potential, pH, and electrical conductivity were evaluated and reassessed after 30 days and 1 year to determine formulation stability. The in vivo anti-inflammatory effect of the EO and LEO was examined using a carrageenan-induced rat paw edema model. Results: The Pinus halepensis EO contained 14 components, mainly, α-pinene, myrcene, and (E)-caryophyllene. Encapsulation efficiency was 97.35%. AFM analyses confirmed the nanoscale dimensions and spherical shape of liposomes, while FTIR indicated successful encapsulation through overlapping functional groups. The droplet size of blank liposomes (L) ranged from 197.4 to 217 nm, while adding the EO decreased the droplet size and electrical conductivity. The polydispersity index (PDI) remained below 0.2. The zeta potential of the liposomes was between −35.61 and −49.43 mV, while the pH value was in the range of 4.35 to 5.01. These results indicate satisfactory stability across repeated measurements. Administration of LEO significantly inhibited paw edema relative to the controls, with a percentage inhibition of approximately 69%, which does not significantly differ from the effect of hydrocortisone, which was used as a positive control. Conclusions: This is the first study to report liposomal encapsulation and in vivo anti-inflammatory activity of an EO derived specifically from green cones of P. halepensis. Our findings demonstrate that EO-loaded liposomes exhibited favorable physico-chemical properties and notable anti-inflammatory activity, comparable to that of hydrocortisone. These results support their potential application in the development of effective topical anti-inflammatory formulations. Full article
(This article belongs to the Special Issue Natural Bioactive Compounds in Micro- and Nanocarriers)
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21 pages, 2216 KB  
Article
Microfluidic Assembly of Poly(glutamic acid) Nanogels Through SPAAC Click Chemistry
by Pasquale Mastella and Stefano Luin
Pharmaceutics 2025, 17(9), 1150; https://doi.org/10.3390/pharmaceutics17091150 - 2 Sep 2025
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Abstract
Background/Objectives: Nanogels (NGs) are promising carriers for drug delivery due to their tunable size, biocompatibility, and capability to encapsulate sensitive molecules. However, conventional batch synthesis often lacks control over key parameters, such as size distribution and encapsulation efficiency. This study aimed to develop [...] Read more.
Background/Objectives: Nanogels (NGs) are promising carriers for drug delivery due to their tunable size, biocompatibility, and capability to encapsulate sensitive molecules. However, conventional batch synthesis often lacks control over key parameters, such as size distribution and encapsulation efficiency. This study aimed to develop a microfluidic platform for the reproducible synthesis of poly(α-glutamic acid) (PGA)-based NGs using strain-promoted azide–alkyne cycloaddition (SPAAC) click chemistry and to investigate the effects of flow parameters on the physicochemical properties of nanogels. Methods: Functionalized PGAs (with azide and DBCO) were co-injected into a microfluidic system within a flux of acetone to form NGs via SPAAC. Flow rate ratios (FRR) and total flow rates were systematically screened at 25 °C, with tests at 50 °C. We evaluated the particle size, polydispersity index (PDI), zeta potential, and encapsulation efficiency (EE%) of doxorubicin-loaded NGs. Results: NGs with tunable sizes ranging from ~50 nm to >170 nm and low PDI (<0.1 in optimal conditions) were obtained. Higher FRR and total flow rates yielded smaller and more uniform NGs. Doxorubicin loading did not affect the nanogel size and uniformity, and in some cases, it improved them. The EE% reached up to ~65%, and ~40% for the best formulations. Elevated temperature improved the characteristics of drug-loaded nanogels at intermediate solvent ratios. Compared to batch synthesis, the microfluidic process offers enhanced reproducibility and size control. Conclusions: Microfluidic SPAAC synthesis enables precise and scalable fabrication of PGA NGs with controllable size and drug loading. This platform supports future integration of on-chip purification and monitoring for clinical nanomedicine applications. Full article
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17 pages, 1931 KB  
Article
Improvement in the Stability of Perilla Seed Oil Microemulsion and Its Role in Fat Accumulation Reduction in Caenorhabditis elegans
by Junwei Pan, Yunzhou Tang, Ziqing Liang, Yong Cao and Yunjiao Chen
Colloids Interfaces 2025, 9(5), 56; https://doi.org/10.3390/colloids9050056 - 30 Aug 2025
Viewed by 480
Abstract
Perilla seed oil (PSO) possesses various physiological functions, such as lowering blood lipids and preventing cancer; however, its poor water solubility, dispersibility, and oxidative stability severely limit its application scope. Epigallocatechin gallate (EGCG) is a natural antioxidant abundant in tea leaves. In this [...] Read more.
Perilla seed oil (PSO) possesses various physiological functions, such as lowering blood lipids and preventing cancer; however, its poor water solubility, dispersibility, and oxidative stability severely limit its application scope. Epigallocatechin gallate (EGCG) is a natural antioxidant abundant in tea leaves. In this study, PSO–casein–EGCG microemulsions were prepared, and their stability and lipid-lowering effects were evaluated. The results showed that the PSO microemulsion had a particle size of 361.23 ± 14.85 nm, a zeta potential of −20.77 ± 0.68 mV, a polydispersity index (PDI) of 0.17 ± 0.07, and an encapsulation efficiency of 94.3%. PSO microemulsions remained stable at room temperature for 5 days without droplet aggregation. The stability of the microemulsions was good when the NaCl concentration was between 0.1 and 1 mM and the pH was between 5 and 9. PSO microemulsions enhanced the oxidative stability of PSO. Additionally, PSO microemulsions significantly reduced triglyceride levels in Caenorhabditis elegans (77.50%, p < 0.005). Finally, it was found that the average lipid droplet size of ZXW618 mutant nematodes decreased by 41.23% after PSO microemulsion treatment. Therefore, PSO microemulsions may reduce fat accumulation in C. elegans by decreasing lipid droplet size. This provides new insights for advancing the application of PSO in the food processing industry. Full article
(This article belongs to the Special Issue Recent Advances on Emulsions and Applications: 3rd Edition)
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29 pages, 4254 KB  
Article
Comparative Study of Natamycin Encapsulation in Liposomes: Thin-Film vs. Proliposome Methods for Enhanced Stability, Controlled Release, and Efficacy Against Milk Spoilage and Pathogenic Microorganisms
by Natalija Čutović, Petar Batinić, Tatjana Marković, Jovana Petrović, Milena Obradović, Branko Bugarski and Aleksandra A. Jovanović
Foods 2025, 14(17), 3064; https://doi.org/10.3390/foods14173064 - 30 Aug 2025
Viewed by 876
Abstract
The aim of this study was to evaluate liposomal particles as a potential delivery system for natamycin, a widely known antimicrobial agent used in the food industry. The goal was to prolong its diffusion into the surrounding medium. Natamycin-loaded liposomes were prepared using [...] Read more.
The aim of this study was to evaluate liposomal particles as a potential delivery system for natamycin, a widely known antimicrobial agent used in the food industry. The goal was to prolong its diffusion into the surrounding medium. Natamycin-loaded liposomes were prepared using two methods (proliposome and thin-film) and two different phospholipid mixtures. The characterization of natamycin-loaded liposomes was performed in terms of their chemical composition (FT-IR analysis), encapsulation efficiency (EE), and antimicrobial potential against spoilage and pathogenic microorganisms that can be found in milk and milk products. During the 60-day storage period, their size, polydispersity index (PDI), and zeta potential were measured. The in vitro release kinetics of natamycin from liposomes were also assessed, and the results showed a significantly lower release rate of the drug when it was encapsulated. EE showed a high level of natamycin encapsulation (>80%), which was confirmed with FT-IR analysis. The stability study indicated that these systems were stable over a 60-day storage period, as the zeta potential of all formulations was ~−25 mV. Satisfactory antimicrobial performance of the developed liposomes against Listeria monocytogenes, Yersinia enterocolitica, Candida tropicalis, Candida parapsilosis, and Aspergillus flavus (MIC values from 0.00625 to 4 mg/mL) indicates that loading of natamycin into liposomal carriers was an adequate method for their encapsulation and delivery in the milk industry. Full article
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