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22 pages, 2852 KiB  
Article
Influence of Supercritical Fluid Extraction Process on Techno-Functionality of Enzymatically Derived Peptides from Filter-Pressed Shrimp Waste
by Narjes Badfar, Ali Jafarpour, Federico Casanova, Lucas Sales Queiroz, Adane Tilahun Getachew, Charlotte Jacobsen, Flemming Jessen and Nina Gringer
Mar. Drugs 2025, 23(3), 122; https://doi.org/10.3390/md23030122 - 11 Mar 2025
Abstract
This study explored how combining supercritical fluid extraction (SFE) and enzymatic hydrolysis influences the structure and functionality of peptides recovered from filter-pressed shrimp waste. Freeze-dried press cake (PC) was defatted via SFE and hydrolyzed using Alcalase (ALC) and trypsin (TRYP). ALC-treated PC achieved [...] Read more.
This study explored how combining supercritical fluid extraction (SFE) and enzymatic hydrolysis influences the structure and functionality of peptides recovered from filter-pressed shrimp waste. Freeze-dried press cake (PC) was defatted via SFE and hydrolyzed using Alcalase (ALC) and trypsin (TRYP). ALC-treated PC achieved the highest protein recovery (63.49%), extraction yield (24.73%), and hydrolysis degree (18.10%) (p < 0.05). SFE-treated hydrolysates showed higher zeta potential (−47.23 to −49.93 mV) than non-SFE samples (−25.15 to −38.62 mV) but had larger droplet sizes, indicating lower emulsion stability. SC-ALC displayed reduced fluorescence intensity and a red shift in maximum wavelength. TRYP hydrolysates reduced interfacial tension (20 mN/m), similar to sodium caseinate (Na-Cas, 13 mN/m), but with lesser effects. Dilatational rheology showed TRYP hydrolysates formed stronger, solid-like structures. These results emphasize protease efficacy over SFE for extracting functional compounds, enhancing shrimp waste valorization. Full article
(This article belongs to the Special Issue Marine-Derived Ingredients for Functional Foods)
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Figure 1

Figure 1
<p>Size exclusion chromatograms illustrating the profiles of shrimp shell hydrolysates (SPHs) obtained without or after supercritical fluid extraction (SFE). (<span style="color:red">—</span>PC-ALC <span style="color:#FFC000">—</span>SC-ALC, <span style="color:#0070C0">—</span>PC-TRYP <span style="color:#00B050">—</span>SC-TRYP).</p>
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<p>Intrinsic fluorescence of SPHs without and after SFE. (<span style="color:red">—</span>PC-ALC <span style="color:#FFC000">—</span>SC-ALC, <span style="color:#0070C0">—</span>PC-TRYP <span style="color:#00B050">—</span>SC-TRYP). The normalized version of Intrinsic fluorescence is available in the <a href="#app1-marinedrugs-23-00122" class="html-app">supplementary file as Figure S1</a>.</p>
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<p>Interfacial tension (IFT) of shrimp shell protein hydrolysates (SPHs). (<span style="color:red">—</span>PC-ALC <span style="color:#F4EE00">—</span>SC-ALC, <span style="color:#0070C0">—</span>PC-TRYP <span style="color:#00B050">—</span>SC-TRYP), sodium caseinate (<span style="color:#ED7D31">—</span>Na-Cas) as positive control and (<span style="color:#00B0F0">—</span>W/O) water in oil droplet.</p>
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<p>Amplitude sweep test of shrimp shell hydrolysates (SPHs) and controls. (<span style="color:red">—</span>PC-ALC <span style="color:#F4EE00">—</span>SC-ALC <span style="color:#0070C0">—</span>PC-TRYP <span style="color:#00B050">—</span>SC-TRYP), sodium caseinate (<span style="color:#ED7D31">—</span>Na-Cas) as positive control and (<span style="color:#00B0F0">—</span>W/O) water in oil droplet. Elastic modulus (E′) is represented with symbol line and viscous modulus (E″) is represented with dotted line.</p>
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<p>Phase angle of shrimp shell hydrolysates (SPHs) and controls. (<span style="color:red">—</span>PC-ALC <span style="color:#F4EE00">—</span>SC-ALC, <span style="color:#0070C0">—</span>PC-TRYP <span style="color:#00B050">—</span>SC-TRYP), sodium caseinate (<span style="color:#ED7D31">—</span>Na-Cas) as positive control and (<span style="color:#00B0F0">—</span>W/O) water in oil droplet.</p>
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<p>Frequency sweep test of shrimp shell hydrolysates (SPHs). (<span style="color:red">—</span>PC-ALC <span style="color:#F4EE00">—</span>SC-ALC, <span style="color:#0070C0">—</span>PC-TRYP <span style="color:#00B050">—</span>SC-TRYP), sodium caseinate (<span style="color:#ED7D31">—</span>Na-Cas) as positive control and (<span style="color:#00B0F0">—</span>W/O) water in oil droplet. Elastic modulus (E′) is represented with symbol line and viscous modulus (E″) is represented with dotted line.</p>
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<p>Lissajous plots of 0.1% SPHs, Na-CAS solution (positive control), and water-in-oil droplet (W/O) under 5, 13.75, 22.5, 31.25, and 40% amplitude.</p>
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<p>Creaming index of emulsions stabilized with 0.2% protein of SPHs and Na-Cas. (<span style="color:red">—</span>PC-ALC <span style="color:#F4EE00">—</span>SC-ALC, <span style="color:#0070C0">—</span>PC-TRYP <span style="color:#00B050">—</span>SC-TRYP <span style="color:#ED7D31">—</span>Na-Cas).</p>
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16 pages, 4731 KiB  
Article
Impact of Dehydration Processing on Scallop (Patinopecten yessoensis) Adductor Muscle: Structural and Oxidative Insights
by Huaqiong Li, Yulong Zhao, Jian Shi, Manat Chaijan, Xichang Wang and Mingyu Yin
Foods 2025, 14(6), 948; https://doi.org/10.3390/foods14060948 - 11 Mar 2025
Viewed by 24
Abstract
This study investigated the impact of four drying techniques—hot air drying (HAD), vacuum hot air drying (VFAD), microwave drying (MWD), and vacuum freeze-drying (VFD)—on the structural, physicochemical, and functional properties of scallop adductor muscles, a critical marine resource in the food industry. The [...] Read more.
This study investigated the impact of four drying techniques—hot air drying (HAD), vacuum hot air drying (VFAD), microwave drying (MWD), and vacuum freeze-drying (VFD)—on the structural, physicochemical, and functional properties of scallop adductor muscles, a critical marine resource in the food industry. The results demonstrated that VFD optimally preserved the ultrastructural integrity of the tissue, maintaining its surface fibrous architecture and achieving a superior recovery ration (78%) and rehydration ration (186.5%) compared to HAD, VFAD, and MWD. While the zeta potential remained statistically invariant across methods, HAD induced the largest particle agglomeration, followed by MWD. Notably, VFD enhanced protein stability, increasing the sulfhydryl content by 163.2% and reducing carbonyl formation by 48.1% relative to HAD, whereas MWD had the opposite effect. Multispectral analyses revealed the severe disruption of protein secondary and tertiary structures after MWD, while VFD minimized conformational denaturation. Statistical modeling ranked the drying sensitivity parameters as follows: surface hydrophobicity > hardness> β-turn content > dityrosine crosslinking > transverse relaxation time T23. These findings underscore VFD as the optimal method for mitigating structural degradation and oxidative damage in scallop processing, providing actionable insights to enhance the technofunctional quality of shelf-stable scallop products. Full article
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Graphical abstract
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<p>Effects of different drying methods on (<b>A</b>) rehydration ratio, (<b>B</b>) recovery rate, (<b>C</b>) water activity, (<b>D</b>) appearance, (<b>E</b>) moisture distribution, and (<b>F</b>) microstructure of scallop <span class="html-italic">Patinopecten yessoensis</span>. Abbreviation: HAD, hot air drying group; VHAD, vacuum hot air drying group; MWD, microwave drying group; VFD, vacuum freeze-drying group; Aw, water activity. The significant difference at <span class="html-italic">p</span> &lt; 0.05 determined by ANOVA (Dun-can’s test). * <span class="html-italic">p</span> or # <span class="html-italic">p</span> &lt; 0.05. ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> or ### <span class="html-italic">p</span> &lt; 0.001 represent significant difference compared to groups determined by Student’s <span class="html-italic">t</span>-test.</p>
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<p>Effects of different drying methods on (<b>A</b>) solubility, (<b>B</b>) turbidity, (<b>C</b>) surface hydrophobic properties, (<b>D</b>) sulfhydryl content, (<b>E</b>) carbonyl content, and (<b>F</b>) dityrosine of scallop <span class="html-italic">Patinopecten yessoensis</span>. Abbreviation: HAD, hot air drying group; VHAD, vacuum hot air drying group; MWD, microwave drying group; VFD, vacuum freeze-drying group. The significant difference at <span class="html-italic">p</span> &lt; 0.05 determined by ANOVA (Duncan’s test). * <span class="html-italic">p</span> or # <span class="html-italic">p</span> &lt; 0.05. ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> or ### <span class="html-italic">p</span> &lt; 0.001 represent significant difference compared to groups determined by Student’s <span class="html-italic">t</span>-test.</p>
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<p>Effects of different drying methods on (<b>A</b>) second-order derivative mapping of UV absorption spectra, (<b>B</b>) fluorescence spectrum, (<b>C</b>) infrared spectrum, (<b>D</b>) infrared second-order derivative fitting curve, and (<b>E</b>) relative content of protein secondary structure of scallop <span class="html-italic">Patinopecten yessoensis</span> myofibrillar protein. Abbreviation: HAD, hot air drying group; VHAD, vacuum hot air drying group; MWD, microwave drying group; VFD, vacuum freeze-drying group. The significant difference at <span class="html-italic">p</span> &lt; 0.05 determined by ANOVA (Duncan’s test). <sup>a,b,c,d</sup> Means in the same column with different superscripts differ significantly (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Effects of different drying methods on (<b>A</b>) protein molecular weight, (<b>B</b>) zeta potential, and (<b>C</b>) particle size distribution of scallop <span class="html-italic">Patinopecten yessoensis</span> myofibrillar protein. Abbreviation: HAD, hot air drying group; VHAD, vacuum hot air drying group; MWD, microwave drying group; VFD, vacuum freeze-drying group. The significant difference at <span class="html-italic">p</span> &lt; 0.05 determined by ANOVA (Duncan’s test). * <span class="html-italic">p</span> &lt; 0.05. ** <span class="html-italic">p</span> &lt; 0.01, ### <span class="html-italic">p</span> &lt; 0.001 represent significant difference compared to groups determined by Student’s <span class="html-italic">t</span>-test. <sup>a,b,c</sup> Means in the same column with different superscripts differ significantly (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Structural and oxidation properties of scallop (<span class="html-italic">Patinopecten yessoensis</span>) adductor muscle. (<b>A</b>) Principal component analysis; (<b>B</b>) Loading plot; (<b>C</b>) VIP value; (<b>D</b>) Top 25 compounds correlated with the Aw; (<b>E</b>) Top 25 compounds correlated with the Rehydration ratio; (<b>F</b>) Top 25 compounds correlated with the Recovery ratio; (<b>G</b>) Correlation heat map; and (<b>H</b>) Spatial network correlation. (Abbreviation: HAD, hot air drying group; VHAD, vacuum hot air drying group; MWD, microwave drying group; VFD, vacuum freeze-drying group; glycine, Gly; arginine, Arg; leucine, Leu; valine, Val; alanine, Ala; serine, Ser; proline, Pro; isoleucine, Ile; phenylalanine, Phe; lysine, Lys; threonine, Thr; methionine, Met; histidine, His; tyrosine acid, Tyr; aspartic acid, Asp; cysteine, Cys; glutamic acid, Glu).</p>
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13 pages, 10303 KiB  
Proceeding Paper
Nano-Encapsulated Ebastine Niosomal Transdermal Nanogel: QBD Model for Allergy Treatment and Evaluation
by Bhushan R. Rane, Aditi P. Padave and Ashish S. Jain
Biol. Life Sci. Forum 2024, 38(1), 9; https://doi.org/10.3390/blsf2024038009 - 11 Mar 2025
Viewed by 31
Abstract
Niosomes are a stable vesicular system composed of non-ionic surfactants and cholesterol, offering advantages such as enhanced stability and controlled drug release. In this study, a niosomal nanogel loaded with Ebastine was developed to improve patient compliance in treating skin allergic reactions. Thin-film [...] Read more.
Niosomes are a stable vesicular system composed of non-ionic surfactants and cholesterol, offering advantages such as enhanced stability and controlled drug release. In this study, a niosomal nanogel loaded with Ebastine was developed to improve patient compliance in treating skin allergic reactions. Thin-film hydration was employed to prepare niosomes using cholesterol, Span 60, Tween 80, and Ebastine, optimized via Box–Behnken experimental design. A dispersion method incorporating Carbopol 934 was utilized to create a niosomal gel, ensuring effective therapeutic outcomes. The formulation exhibited high drug entrapment efficiency (84.19%), a zeta potential of −27 mV, and vesicle sizes ranging from 100 to 300 nm. Evaluation included FTIR for drug–excipient compatibility, pH assessment, in vitro drug release studies, and stability testing, all yielding acceptable results. The encapsulation of Ebastine within niosomes is driven by critical physicochemical interactions between the drug, cholesterol, and surfactants. These interactions influence the stability, encapsulation efficiency, and release profile of the drug from the niosomal bilayer. Microbial studies indicated significant antimicrobial activity against S. aureus, underscoring its potential as an effective transdermal treatment for skin allergies. Full article
(This article belongs to the Proceedings of The 4th International Electronic Conference on Nutrients)
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Figure 1
<p>Schematic representation of the thin film hydration method.</p>
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<p>FTIR spectra of (A) pure-drug Ebastine and (B) optimized formulation.</p>
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<p>Contour plots and response surface of entrapment efficiency.</p>
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<p>Contour plots and response surface of zeta potential.</p>
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<p>Contour plots and response surface of vesicle size.</p>
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<p>TEM image of niosomal vesicles.</p>
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<p>(<b>A</b>) Particle size and PDI; (<b>B</b>) zeta potential of optimized niosomal nanogel formulation.</p>
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<p>In vitro antimicrobial activity; (<b>A</b>) <span class="html-italic">S. aureus</span> (EBT) (<b>B</b>) <span class="html-italic">S. aureus</span> (niosomal gel).</p>
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<p>Comparative study.</p>
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32 pages, 5767 KiB  
Article
Green Synthesis of Silver Nanoparticles Using Paullinia cupana Kunth Leaf Extract Collected in Different Seasons: Biological Studies and Catalytic Properties
by Alan Kelbis Oliveira Lima, Ítalo Rennan Sousa Vieira, Lucas Marcelino dos Santos Souza, Isadora Florêncio, Ingrid Gracielle Martins da Silva, Alberto Gomes Tavares Junior, Yasmin Alves Aires Machado, Lucas Carvalho dos Santos, Paulo Sérgio Taube, Gerson Nakazato, Laila Salmen Espindola, Lorena Carneiro Albernaz, Klinger Antônio da França Rodrigues, Marlus Chorilli, Hugo de Campos Braga, Dayane Batista Tada, Sônia Nair Báo, Luís Alexandre Muehlmann and Mônica Pereira Garcia
Pharmaceutics 2025, 17(3), 356; https://doi.org/10.3390/pharmaceutics17030356 - 10 Mar 2025
Viewed by 97
Abstract
Background: Paullinia cupana Kunth, popularly known as guarana, a native Amazonian shrub cultivated by the Sateré-Mawé ethnic group, has been used in traditional medicine for various purposes, including stimulant and therapeutic actions, due to its chemical composition, which is rich in bioactive [...] Read more.
Background: Paullinia cupana Kunth, popularly known as guarana, a native Amazonian shrub cultivated by the Sateré-Mawé ethnic group, has been used in traditional medicine for various purposes, including stimulant and therapeutic actions, due to its chemical composition, which is rich in bioactive compounds. This study explored the reductive potential of guarana with nanobiotechnology and aimed to synthesize silver nanoparticles (AgNPs) using the aqueous extract of leaves collected during the dry and rainy seasons, assessing their biological and catalytic activities. Methods: The AgNPs were synthesized in a water bath at 70 °C for three hours and then characterized using techniques such as UV-Vis spectroscopy, DLS, zeta potential, MET, NTA, and EDX and had their effects on various biological systems assessed in vitro, as well as in catalytic tests aimed at indicating the probable influence of the time when the plant material was collected on the properties of the nanostructures. Results: The AgNPs had an average diameter between 39.33 and 126.2 nm, spherical morphology, absorption bands between 410 and 450 nm, and high colloidal stability over two years. The biological results showed antibacterial activity against all the species tested, as well as remarkable antioxidant action against DPPH and ABTS free radicals, in the same way as the aqueous leaf extracts of P. cupana, in addition to cytotoxic properties against cancerous (A431 and A549) and non-cancerous (HaCaT and HNTMC) cells. The AgNPs were active against promastigote forms of Leishmania (Leishmania) amazonensis while not affecting the viability of macrophages, and from the LC50 and LC90 values, the AgNPs were more effective than the metal salt solution in controlling Aedes aegypti larvae and pupae. We also reported that the catalytic degradation of the organic dyes methylene blue (MB) and methyl orange (MO) by AgNPs was over 90% after 40 or 14 min, respectively. Conclusions: Thus, our results support the potential of seasonal extracts of guarana leaves to produce AgNPs with diverse application possibilities for the health, industrial, and environmental sectors. Full article
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<p>Visual recording of the 2 mM silver nitrate solutions, plant extracts from <span class="html-italic">Paullinia cupana</span> leaves, and biogenic AgNPs.</p>
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<p>Kinetic curves for the synthesis of AgNPs and their experimental controls obtained by spectrophotometric analysis at 450 nm for 180 min of reaction.</p>
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<p>Absorption curves of AgNPs and their experimental controls measured by spectrophotometry in the 350–550 nm range after 180 min of reaction.</p>
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<p>TEM micrographs at 10,000× magnification and histograms of the dry diameter distribution of (<b>A</b>) AgNPs-LD and (<b>B</b>) AgNPs-LR.</p>
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<p>EDX spectra and elemental map showing the distribution of the atoms present in the samples (<b>A</b>) AgNPs-LD and (<b>B</b>) AgNPs-LR.</p>
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<p>Antioxidant activity of AgNPs, plant extracts of <span class="html-italic">Paullinia cupana</span> leaves collected in the dry and rainy seasons, and aqueous ascorbic acid (AA) solution against the DPPH free radical. The different letters indicate statistical significance (<span class="html-italic">p</span> &lt; 0.05) between the treatments within each test concentration. On the X axis, the upper line indicates the test concentrations of AgNPs and AA. The lower line indicates the test concentrations of the plant extracts of <span class="html-italic">Paullinia cupana</span> leaves.</p>
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<p>Antioxidant activity of AgNPs, plant extracts of <span class="html-italic">Paullinia cupana</span> leaves collected in the dry and rainy seasons, and aqueous ascorbic acid (AA) solution against the ABTS free radical. The different letters indicate statistical significance (<span class="html-italic">p</span> &lt; 0.05) between the treatments within each test concentration. On the X axis, the upper line indicates the test concentrations of AgNPs and AA. The lower line indicates the test concentrations of the plant extracts of <span class="html-italic">Paullinia cupana</span> leaves.</p>
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<p>Viability graphs of the cell lines (<b>A</b>) A431, (<b>B</b>) HaCaT, (<b>C</b>) A549, and (<b>D</b>) HNTMC after incubation with AgNPs, plant extracts of <span class="html-italic">Paullinia cupana</span> leaves collected in the dry and rainy seasons, and aqueous AgNO<sub>3</sub> solution. On the X axis, the top line indicates the test concentrations of AgNPs and AgNO<sub>3</sub>. The lower line indicates the test concentrations of the <span class="html-italic">Paullinia cupana</span> leaf extracts.</p>
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<p>Catalytic degradation of methylene blue dye (MB): (<b>A</b>) UV-Vis absorption spectra with the NaBH<sub>4</sub> substrate only; (<b>B</b>) images of aqueous solutions of MB in the absence and presence of AgNPs (<b>C</b>) UV-Vis spectra with NaBH<sub>4</sub> and the AgNPs-LD; and (<b>D</b>) AgNPs-LR nanocatalysts.</p>
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<p>Catalytic degradation of methyl orange dye (MO): (<b>A</b>) UV-Vis absorption spectra with the NaBH<sub>4</sub> substrate only; (<b>B</b>) images of aqueous solutions of MO in the absence and presence of AgNPs (<b>C</b>) UV-Vis spectra with NaBH<sub>4</sub> and the AgNPs-LD; and (<b>D</b>) AgNPs-LR nanocatalysts.</p>
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18 pages, 1159 KiB  
Article
Parenteral Nanoemulsion for Optimized Delivery of GL-II-73 to the Brain—Comparative In Vitro Blood–Brain Barrier and In Vivo Neuropharmacokinetic Evaluation
by Kristina Jezdić, Jelena Đoković, Ivan Jančić, Tanja Ilić, Biljana Bufan, Bojan Marković, Jana Ivanović, Tijana Stanković, Nebojša D. Cekić, Vassiliki Papadimitriou, Dishary Sharmin, Prithu Mondal, James M. Cook, Snežana D. Savić and Miroslav M. Savić
Pharmaceutics 2025, 17(3), 354; https://doi.org/10.3390/pharmaceutics17030354 - 10 Mar 2025
Viewed by 219
Abstract
Background/Objectives: GL-II-73 is a positive allosteric modulator that is selective for α5GABAA receptors and has physicochemical properties that favor nanocarrier formulations when parenteral delivery to the central nervous system is desired. Our aim was to develop an optimized nanoemulsion containing GL-II-73 [...] Read more.
Background/Objectives: GL-II-73 is a positive allosteric modulator that is selective for α5GABAA receptors and has physicochemical properties that favor nanocarrier formulations when parenteral delivery to the central nervous system is desired. Our aim was to develop an optimized nanoemulsion containing GL-II-73 and subsequently test whether this would improve permeation across the blood–brain barrier (BBB) and availability in the brain. Methods: The nanoemulsions were formulated and subjected to detailed physiochemical characterization. The optimized formulation was tested in comparison to a solution of GL-II-73 in the appropriate solvent in an in vitro model of the blood–brain barrier based on human induced pluripotent stem cell-derived microvascular endothelial cells, astrocytes, and pericytes. Plasma and brain exposure to GL-II-73 and its metabolite MP-III-022 was investigated in an in vivo neuropharmacokinetic study in rats exposed to the selected nanoemulsion and the conventional solution formulation. Results: The selected biocompatible nanoemulsion exhibited satisfactory physicochemical properties for parenteral administration, with a Z-ave of 122.0 ± 1.5, PDI of 0.123 ± 0.009 and zeta potential of −40.7 ± 1.5, pH of 5.16 ± 0.04, and adequate stability after one year of storage, and allowed the localization of GL-II-73 in the stabilization layer. The permeability of GL-II-73 through the BBB was twice as high with the selected nanoemulsion as with the solution. The availability of GL-II-73 and MP-III-022 (also a positive allosteric modulator selective for α5GABAA receptors) in the brain was 24% and 61% higher, respectively, after intraperitoneal administration of the nanoemulsion compared to the solution; the former increase was statistically significant. Conclusions: The increased permeability in vitro proved to be a good predictor for the improved availability of GL-II-73 in brain tissue in vivo from the formulation obtained by encapsulation in a nanoemulsion. The putative additive effect of the parent molecule and its metabolite MP-III-022 could lead to enhanced and/or prolonged modulation of α5GABAA receptors in the brain. Full article
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<p>Chemical structures of GL-II-73 and its mono-demethyl metabolite MP-III-022.</p>
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<p>EPR spectra of the optimized NE4 nanoemulsion in (<b>a</b>) 5-DSA and (<b>b</b>) 16-DSA spin probes.</p>
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<p>Plasma concentration–time profile of GL-II-73 and MP-III-022 and calculated pharmacokinetic parameters after intraperitoneal administration of 10 mg/kg dose of GL-II-73 nanoemulsion or solution (<span class="html-italic">n</span> = 3 per time point). (C<sub>max</sub> = maximum concentration in plasma; T<sub>max</sub> = time of maximum concentration in plasma; t<sub>1/2</sub> = terminal elimination half-life from plasma; AUC<sub>0-36</sub> = area under the plasma concentration–time curve from 0 to 36 h; means ± SD, <span class="html-italic">n</span> = 3). * and ***, <span class="html-italic">p</span> &lt; 0.05 and <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Brain concentration–time profile of GL-II-73 and MP-III-022 and calculated pharmacokinetic parameters after intraperitoneal administration of 10 mg/kg dose of GL-II-73 nanoemulsion or solution (<span class="html-italic">n</span> = 3 per time point). (C<sub>max</sub> = maximum concentration in brain; Tmax = time of maximum concentration in brain; t<sub>1/2</sub> = elimination half-life from brain; AUC<sub>0-36</sub> = area under the brain concentration–time curve from 0 to 36 h; means ± SD, <span class="html-italic">n</span> = 3). *, <span class="html-italic">p</span> &lt; 0.05.</p>
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16 pages, 2467 KiB  
Article
Photosensitized Methylene Blue Nanoparticles: A Promising Approach for the Control of Oral Infections
by Magali Parizzi, Aline Rosa Almeida, Gabriel Salvador, Diogo Dominguini, Mylena Fernandes, Daniela Becker, Michael Ramos Nunes, Anelise Viapiana Masiero and Cleonice Gonçalves da Rosa
Biomedicines 2025, 13(3), 673; https://doi.org/10.3390/biomedicines13030673 - 10 Mar 2025
Viewed by 175
Abstract
Introduction: Oral infections pose significant public health challenges, often exacerbating other comorbidities and increasing systemic health risks. Traditional treatments often fail to eliminate persistent micro-organisms and contribute to the rise of antimicrobial resistance. Nanoparticulate systems offer a promising solution by delivering active agents [...] Read more.
Introduction: Oral infections pose significant public health challenges, often exacerbating other comorbidities and increasing systemic health risks. Traditional treatments often fail to eliminate persistent micro-organisms and contribute to the rise of antimicrobial resistance. Nanoparticulate systems offer a promising solution by delivering active agents directly to targeted sites, providing more effective and localized treatment options. Objective: This study aimed to synthesize and characterize methylcellulose nanoparticles containing methylene blue at different concentrations using the nanoprecipitation method. We also evaluated their biocompatibility and antimicrobial activity against key micro-organisms commonly found in oral infections. Methods: The study involved physicochemical and morphological characterizations, including encapsulation efficiency, particle size, polydispersity index, zeta potential, and transmission electron microscopy (TEM). Additionally, controlled release profiles, antimicrobial efficacy against major oral pathogens, and biocompatibility in vitro assessments were performed. Results: The results revealed encapsulation efficiency between 99.1 and 98.8%, with particle sizes ranging from 186 to 274 nm and a zeta potential of 1.7 to 2.9 mV achieved at lower concentrations of methylene blue and methylcellulose. The nanoparticles demonstrated sustained drug release of 85% for the smaller particles and 45% for the larger particles for more than 10 h. The nanoparticles exhibited superior antimicrobial activity compared to pure methylene blue. Cell viability studies indicated that the nanoparticles were biocompatible with approximately 40% cell viability at lower concentrations of the nanoparticles. Conclusions: These findings suggest that methylene blue nanoparticles could serve as a promising adjunct in dental treatments. They offer targeted antimicrobial action while potentially reducing the development of antimicrobial resistance. Full article
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<p>Particle size distribution and zeta potential. (<b>a</b>,<b>b</b>) MC 0.001-MB 0.005; (<b>c</b>,<b>d</b>) MC 0.005-MB 0.005; (<b>e</b>,<b>f</b>) MC 0.001-MB free and (<b>g</b>,<b>h</b>) MC 0.005-MB free.</p>
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<p>Micrographs of transmission electron microscopy. (<b>a</b>) MC0.001-MB 0.005 and (<b>b</b>) MC0.005-MB 0.005.</p>
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<p>FTIR spectrum of nanoparticles. (a) MC 0.001-MB 0.005, (b) MC 0.005-MB 0.005, (c) MC 0.001-MB free, (d) MC 0.005-MB free, (e) MC and (f) MB.</p>
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<p>Profile release of methylene blue in methylcellulose matrices.</p>
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<p>Survival of oral mucosa cells against different concentrations of methylene-blue-loaded methylcellulose nanoparticles. (<b>a</b>) MC 0.001-MB 0.005 and (<b>b</b>) MC 0.005-MB 0.005. The <span class="html-italic">p</span> values: * <span class="html-italic">p</span> &lt; 0.05.</p>
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20 pages, 7081 KiB  
Article
Albumin-Based Nanoparticles with Factorial Design as a Promising Approach for Remodeled Repaglinide: Evidence from In Silico, In Vitro, and In Vivo Evaluations
by Mennatullah M. Faisal, Eman Gomaa, Mohamed S. Attia, Rana M. Abdelnaby, Adel Ehab Ibrahim, Ahmed Al-Harrasi, Sami El Deeb and Al Zahraa G. Al Ashmawy
Pharmaceutics 2025, 17(3), 350; https://doi.org/10.3390/pharmaceutics17030350 - 9 Mar 2025
Viewed by 241
Abstract
Background/Objectives: Hyperlipidemia is a silent threat lurking in the bloodstream of millions worldwide. The nano-based platform has emerged as a promising drug delivery technology. Repaglinide, an anti-diabetic drug, was investigated recently as an antihyperlipidemic candidate that could supersede the available antihyperlipidemic drugs. Our [...] Read more.
Background/Objectives: Hyperlipidemia is a silent threat lurking in the bloodstream of millions worldwide. The nano-based platform has emerged as a promising drug delivery technology. Repaglinide, an anti-diabetic drug, was investigated recently as an antihyperlipidemic candidate that could supersede the available antihyperlipidemic drugs. Our goal was to optimize albumin-based nanoparticles loaded with Repaglinide for parenteral delivery and conduct in silico and in vivo studies to explore the efficacy of Repaglinide for the management of hyperlipidemia along with its anti-diabetic effect. Methods: The impact of three independent factors, the albumin%, acetone volume, and glutaraldehyde/albumin, on the particle size, zeta potential, and entrapment efficiency was investigated. Results: The optimized formulation was spherical, homogenous of an average diameter (~181.86 nm) with a narrow size distribution, a zeta potential of −24.26 mV, and 76.37% as the EE%. The in vitro release of Repaglinide from nanoparticles showed a sustained release pattern for 168 h, with an initial burst release after 24 h, and was fitted to the Fickian diffusion mechanism. A molecular docking simulation showed a strong affinity to several protein targets, and the results were very promising, where Repaglinide gave a score of −7.70 Kcal/mol compared to Mevastatin (−6.71 Kcal/mol) and Atorvastatin (−8.36 Kcal/mol). On conducting in vivo studies on animal models, the optimized formula recorded a statistically significant decrease in the serum levels of total cholesterol, triglyceride, and low-density lipoproteins, with an increased high-density lipoprotein. Conclusions: This study suggested albumin nanoparticles as potential nanocarriers for the parenteral delivery of Repaglinide to ameliorate its antihyperlipidemic benefits, especially in diabetic patients. Full article
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<p>One factor plots of Y1 response (particle size). (<b>A</b>) Effect of A (albumin %) on Y1; (<b>B</b>) effect of B (Volume of acetone) on Y1; (<b>C</b>) effect of C (µL glutaraldehyde per 2 mg of albumin) on Y1.</p>
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<p>One factor plots of Y2 response (zeta potential). (<b>A</b>) Effect of A (albumin %) on Y2; (<b>B</b>) effect of B (Volume of acetone) on Y2; (<b>C</b>) effect of C (µL glutaraldehyde per 2 mg of albumin) on Y2.</p>
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<p>One factor plots of Y3 response (entrapment efficiency%). (<b>A</b>) Effect of A (albumin %) on Y3; (<b>B</b>) effect of B (Volume of acetone) on Y3; (<b>C</b>) effect of C (µL glutaraldehyde per 2 mg of albumin) on Y3.</p>
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<p>In vitro drug release of Repaglinide from BSA nanoparticles (F1–F8) in SPB solution (pH 7.4) at 37 ± 0.2 °C and 100 rpm for 160 h.</p>
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<p>(<b>a</b>) TEM of the optimized Repaglinide nanoparticles: (F5) (<b>A</b>) 200 nm scale; (<b>B</b>) 50 nm scale. (<b>b</b>) SEM of the optimized Repaglinide nanoparticles: (F5) dried on aluminum foil (<b>A</b>) 4 µm scale; (<b>B</b>) 3 µm scale.</p>
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<p>DSC of (<b>A</b>) pure Repaglinide, (<b>B</b>) BSA, (<b>C</b>) physical mixture of Repaglinide, and (<b>D</b>) optimized Repaglinide nanoparticles (F5).</p>
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13 pages, 4546 KiB  
Article
Efficient and Green Flotation Separation of Molybdenite from Chalcopyrite Using 1-Thioglycerol as Depressant
by Feng Jiang, Shuai He, Wei Sun, Yuanjia Luo and Honghu Tang
Metals 2025, 15(3), 299; https://doi.org/10.3390/met15030299 - 9 Mar 2025
Viewed by 272
Abstract
The effective and environmental separation of chalcopyrite and molybdenite has long presented a challenge in mineral processing due to their similar floatability and close association at room temperature. This study explores the non-toxic 1-thioglycerol (1-TG) as a selective depressant for chalcopyrite–molybdenite flotation separation. [...] Read more.
The effective and environmental separation of chalcopyrite and molybdenite has long presented a challenge in mineral processing due to their similar floatability and close association at room temperature. This study explores the non-toxic 1-thioglycerol (1-TG) as a selective depressant for chalcopyrite–molybdenite flotation separation. An impressive separation effect was realized through single-mineral and mixed-mineral flotation experiments when using 1-TG as a depressant and kerosene as a collector. Contact angle measurements, zeta potential tests, and Fourier transform infrared spectroscopy (FT-IR) confirm the selective adsorption of 1-TG on the chalcopyrite surface, leading to enhanced surface hydrophilicity and the inhibition of collector adsorption. The depression mechanism is further elucidated through X-ray photoelectron spectroscopy (XPS), which demonstrates that it occurs via chemosorption between the thiol group in 1-TG and active iron sites on the chalcopyrite surface. These findings provide a potential efficient depressant for chalcopyrite–molybdenite flotation separation with low dosage, environmental friendliness, and human harmlessness. Full article
(This article belongs to the Special Issue Advances in Flotation Separation and Mineral Processing)
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<p>XRD patterns of (<b>a</b>) chalcopyrite and (<b>b</b>) molybdenite samples.</p>
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<p>Flotation recovery rates of chalcopyrite and molybdenite vary with the (<b>a</b>) concentration of 1-TG and (<b>b</b>) pH value (2.8 × 10<sup>−4</sup> mol/L 1-TG, 2.5 × 10<sup>−4</sup> mol/L kerosene, and 4.5 × 10<sup>−4</sup> mol/L terpineol).</p>
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<p>Recovery rate and grade of flotation concentrate for artificially mixed ore were measured at room temperature.</p>
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<p>Contact angles of chalcopyrite and molybdenite before and after treatment with various reagents.</p>
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<p>Zeta potentials of (<b>a</b>) chalcopyrite and (<b>b</b>) molybdenite versus pH value.</p>
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<p>FT-IR spectra of (<b>a</b>) kerosine and 1-TG; (<b>b</b>) chalcopyrite and (<b>c</b>) molybdenite treated with different reagents.</p>
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<p>(<b>a</b>) Cu 2p<sub>3/2</sub>, (<b>b</b>) Fe 2p<sub>3/2</sub>, and (<b>c</b>) S 2p high-resolution XPS spectra of chalcopyrite.</p>
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<p>(<b>a</b>) Mo 3d and (<b>b</b>) S 2p high-resolution XPS spectra of molybdenite.</p>
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<p>Illustration of the probable adsorption mechanism of 1-TG on chalcopyrite surface.</p>
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15 pages, 3438 KiB  
Article
One-Part Alkali-Activated Wood Biomass Binders for Cemented Paste Backfill
by Kunlei Zhu, Haijun Wang, Lu Dong, Xulin Zhao, Junchao Jin, Yang Liu, Jianbo Liu and Dingchao Lv
Minerals 2025, 15(3), 273; https://doi.org/10.3390/min15030273 - 7 Mar 2025
Viewed by 224
Abstract
This study developed a one-part alkali-activated slag/wood biomass fly ash (WBFA) binder (AAS) for preparing cemented paste backfill (CPB) as an alternative to traditional cement. Through multi-scale characterizations (XRD, FTIR, TGA, rheological testing, and MIP) and performance analyses, the regulation mechanisms of slag/WBFA [...] Read more.
This study developed a one-part alkali-activated slag/wood biomass fly ash (WBFA) binder (AAS) for preparing cemented paste backfill (CPB) as an alternative to traditional cement. Through multi-scale characterizations (XRD, FTIR, TGA, rheological testing, and MIP) and performance analyses, the regulation mechanisms of slag/WBFA ratios on hydration behavior, microstructure, and mechanical properties were systematically revealed. Results demonstrate that high slag proportions significantly enhance slurry rheology and mechanical strength, primarily through slag hydration generating dense gel networks of hydration products and promoting particle aggregation via reduced zeta potential. Although inert components in WBFA inhibit early hydration, the long-term reactivity of slag effectively counteracts these negative effects, achieving comparable 28-day compressive strength between slag/WBFA-based CPB (4.11 MPa) and cement-based CPB (4.16 MPa). Microstructural analyses indicate that the disordered gels in AAS systems exhibit silicon–oxygen bond polymerization degrees (950 cm−1) comparable to cement, while WBFA regulates Ca/Si ratios to induce bridging site formation (900 cm−1), significantly reducing porosity and enhancing structural compactness. This research provides theoretical support and process optimization strategies for developing low-cost, high-performance mine filling materials using industrial solid wastes, advancing sustainable green mining practices. Full article
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<p>SEM image of WBFA.</p>
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<p>Particle size distributions of WBFA and tailings.</p>
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<p>XRD pattern of WBFA. (Q: quartz, H: hematite, G: anhydrite, A: anorthite).</p>
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<p>XRD pattern of CS and AAS pastes cured for 7 days and 60 days. (Q: quartz, E: ettringite, B: blite, C: C–S–H gels).</p>
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<p>(<b>A</b>) TG and (<b>B</b>) DTG curves of CS and AAS pastes cured for 7 and 60 days. Ht: hydratalcite-like phases; CH: portlandite.</p>
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<p>FTIR pattern of CS and AAS pastes cured for 7 days and 60 days.</p>
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<p>(<b>A</b>) Flow spread, yield stress, and (<b>B</b>) zeta potential results of different CPB samples.</p>
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<p>UCS results of samples at different curing times.</p>
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<p>MIP results of S40-CPB and S80-CPB.</p>
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30 pages, 13089 KiB  
Article
Polylactic-Co-Glycolic Acid/Alginate/Neem Oil-Reduced Graphene Oxide as a pH-Sensitive Nanocarrier for Hesperidin Drug Delivery: Antimicrobial and Acute Otitis Media Assessments
by Saeed Abdul Kareem Saeed Al-Zuhairy, Sammar Fathy Elhabal, Mohamed Fathi Mohamed Elrefai, Sandra Hababeh, Jakline Nelson, Marwa Fady, Nahla A. Elzohairy, Tassneim M. Ewedah, Ibrahim S. Mousa and Ahmed Mohsen Elsaid Hamdan
Pharmaceuticals 2025, 18(3), 381; https://doi.org/10.3390/ph18030381 (registering DOI) - 7 Mar 2025
Viewed by 200
Abstract
Background/Objectives: Hesperidin (HSP) is a potent phytochemical antioxidant and anti-inflammatory agent that protects against otitis media. However, due to its low solubility and bioavailability, a suitable delivery method is needed to overcome these problems. A hydrogel is a promising nanocarrier for controlled [...] Read more.
Background/Objectives: Hesperidin (HSP) is a potent phytochemical antioxidant and anti-inflammatory agent that protects against otitis media. However, due to its low solubility and bioavailability, a suitable delivery method is needed to overcome these problems. A hydrogel is a promising nanocarrier for controlled drug delivery in response to external stimuli, such as pH variations. Methods: Graphene oxide (GO)-based nanocarriers that encapsulate hesperidin (HSP) were further coated with a polylactic-co-glycolic acid/alginate (PLGA-Alg) hydrogel before being integrated into a green neem oil (N.O.) double emulsion to produce a synergistic effect and then characterized by different assays. Results: The nanocarriers exhibited a substantial particle size (168 ± 0.32 nm), with high encapsulation (89.86 ± 0.23%) and a zeta potential of 37 ± 0.43 mV. In vitro release studies conducted over 96 h indicated a sustained HSP release of 82% at pH 5.4 and 65% at pH 7.4. The GO-HSP-loaded neem oil double emulsion formulation exhibits substantial antibacterial activity, as evidenced by inhibition zones of 39 ± 0.02 mm against Staphylococcus epidermidis, and considerable antifungal activity against Candida albicans, with an inhibition zone of 43 ± 0.13 mm, along with biofilm inhibition activity. The formulation demonstrated antioxidant activity (5.21 µg/mL) and increased cell viability (90–95%) while maintaining low cytotoxicity in HSE-2 cells. A histopathological analysis confirmed that treatment with the nanocarriers reduced the levels of pro-inflammatory cytokines (IL-1β, TNF-α, TLR4, IL-6) and raised the levels of antioxidant markers (Nrf-2, SOD) in an in vivo rat model of otitis media. Conclusions: GO-based nanocarriers integrated into a neem oil double emulsion and coated with PLGA-Alg hydrogel deliver hesperidin with sustained release and enhanced antibacterial, antifungal, and antioxidant properties. This formulation may be used to treat otitis media and other oxidative stress diseases. Full article
(This article belongs to the Special Issue Progress of Hydrogel Applications in Novel Drug Delivery Platforms)
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<p>GC/MS analysis of the fixed neem oil.</p>
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<p>Three-dimensional compounds identified from GC/MS analysis of fixed neem oil. Note: (<b>1</b>) lauric acid, (<b>2</b>) myristic acid, (<b>3</b>) pentadecanoic acid, (<b>4</b>) palmitic acid, (<b>5</b>) palmitoleic acid, (<b>6</b>) margaric acid, (<b>7</b>) stearic acid, (<b>8</b>) elaidic acid, (<b>9</b>) oleic acid, (<b>10</b>) linolelaidic acid, (<b>11</b>) linoleic acid, (<b>12</b>) linolenic acid, (<b>13</b>) arachidic acid, (<b>14</b>) cis-11-Eicosenoic acid, (<b>15</b>) cis-11,14-eicosadienoic acid, (<b>16</b>) heneicosanoic acid, (<b>17</b>) homo-γ-linolenic acid, (<b>18</b>) behenic acid, (<b>19</b>) tricosanoic acid, and (<b>20</b>) lignoceric acid.</p>
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<p>Transmission electron microscopy (TEM) image of GO.</p>
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<p>(<b>a</b>) SEM image of hydrogel, (<b>b</b>) transform infrared spectroscopy, (<b>c</b>) differential scanning calorimeter, and (<b>d</b>) hesperidin release profile from double nanoemulsion at pH 5.4 and 7.4.</p>
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<p>Drug release data fitted to kinetic drug release models.</p>
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<p>Three-dimensional view and surface mapping of the following: (<b>a</b>) co-crystalized ligand as an activator, which binds with the oleic acid binding domain in PPARα target site; (<b>b</b>) co-crystalized ligand against Toll-like receptor 4 target site; (<b>c</b>) palmitic acid as an activator, which binds with the oleic acid binding domain in PPARα target site; (<b>d</b>) palmitic acid against Toll-like receptor 4 target site; (<b>e</b>) linoleic acid as an activator, which binds with the oleic acid binding domain in PPARα target site; (<b>f</b>) linoleic acid against Toll-like receptor 4 target site.</p>
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<p>(<b>a</b>) The oxidative properties of ascorbic acid, hesperidin with neem oil, and GO-HSPloaded neem oil double emulsion against DPPH. (<b>b</b>) HSE-2 cell viability was determined after a 24 h incubation period using the MTT cell proliferation assay. Each tested cell line underwent three repetitions of the experiments.</p>
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<p>(<b>a</b>) Antibacterial activity of (1) HSP solution, (2) neem oil, (3) HSP with neem oil, (4) hydrogel, and (5) GO-HSP-loaded neem oil double emulsion against <span class="html-italic">Staphylococcus epidermidis</span>, <span class="html-italic">Pseudomonas</span>, <span class="html-italic">Klebsiella pneumoniae</span>, and Escherichia coli; (<b>b</b>–<b>d</b>) antibiofilm reduction and (<b>e</b>) antifungal activity against <span class="html-italic">Candida Albicans</span>.</p>
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<p>G1 is the negative control; G2 is the positive control; G3 was treated with a mixture of HSP and neem oil; G4 received HSP-loaded alginate-PLGA-GO hydrogel; and G5 received a GO-HSP-loaded neem oil double emulsion. Note: (<b>a</b>) Toll-like receptor 4 (TLR4), (<b>b</b>) Interleukin-1 beta (IL-1β), (<b>c</b>) Tumor necrosis factor-alpha (TNF-α), (<b>d</b>) Oxidative Stress Marker, (<b>e</b>) Nuclear factor erythroid 2-related factor 2 (Nrf2), and (<b>f</b>) SOD Superoxide dismutase (SOD), an antioxidant enzyme, * 0.0252, *** 0.0029, and **** &lt;0.0001. n.s. no significant difference.</p>
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<p>G1 is the negative control; G2 is the positive control; G3 was treated with a mixture of HSP and neem oil; G4 received HSP-loaded alginate-PLGA-GO hydrogel; and G5 received a GO-HSP-loaded neem oil double emulsion. (<b>G1</b>) Photomicrograph showing scab formation with infiltration of dermal layer by the high number of neutrophils; (<b>G2</b>) photomicrograph showing the formation of some epidermal layers (arrow) with infiltration by inflammatory cells mainly neutrophils and lymphocytes (star) covered by scab; (<b>G3</b>) photomicrograph showing moderate edema in the dermis; Note: Arrowhead (▲) appears to point to epidermal damage or necrosis, possibly indicating structural damage to the epidermis. Arrow (→) appears to highlight connective tissue alterations or inflammatory infiltration in the dermal layer, which could be due to an immune response or infection. Additionally, the star (★) marks areas of intense inflammatory infiltration (x = 25 µm). (<b>G4</b>) photomicrograph showing moderate edema in the dermis; (<b>G5</b>) photomicrograph showing the normal histological structure of epidermis and dermis (hematoxylin and eosin stain).</p>
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<p>Schematic representation of polylactic-co-glycolic acid/alginate-coated graphene oxide-hesperidin and its encapsulation in a water-in-oil-in-water (W/O/W) dual emulsion containing neem oil.</p>
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27 pages, 5680 KiB  
Article
Synergistic Effects of Green Nanoparticles on Antitumor Drug Efficacy in Hepatocellular Cancer
by Mirela Claudia Rîmbu, Liliana Popescu, Mirela Mihăilă, Roxana Colette Sandulovici, Daniel Cord, Carmen-Marinela Mihăilescu, Mona Luciana Gălățanu, Mariana Panțuroiu, Carmen-Elisabeta Manea, Adina Boldeiu, Oana Brîncoveanu, Mihaela Savin, Alexandru Grigoroiu, Florin Dan Ungureanu, Emilia Amzoiu, Mariana Popescu and Elena Truță
Biomedicines 2025, 13(3), 641; https://doi.org/10.3390/biomedicines13030641 - 5 Mar 2025
Viewed by 374
Abstract
Background/Objectives: Cancer remains one of the leading causes of mortality worldwide. Despite significant advancements in treatment strategies and drug development, survival rates remain low and the adverse effects of conventional therapies severely impact patients’ quality of life. This study evaluates the therapeutic [...] Read more.
Background/Objectives: Cancer remains one of the leading causes of mortality worldwide. Despite significant advancements in treatment strategies and drug development, survival rates remain low and the adverse effects of conventional therapies severely impact patients’ quality of life. This study evaluates the therapeutic potential of plant-derived extracts in hepatocellular carcinoma treatment, with a focus on minimizing side effects while enhancing efficacy. Methods: This research investigates the in vitro synergistic effect of silver bio-nanoparticles synthesized from Clematis vitalba, Melissa officinalis, and Taraxacum officinale extracts (Clematis vitalbae extractum—CVE, Melissae extractum—ME, Taraxaci extractum—TE) in combination with liver cancer drugs, sunitinib (SNTB) and imatinib (IMTB), on HepG2 (human hepatocellular carcinoma) and HUVEC (human umbilical vein endothelial) cell lines. The silver nanoparticles (AgNPs) were characterized using UV-Vis spectroscopy, dynamic light scattering (DLS), zeta potential analysis, and scanning electron microscopy (SEM). The antitumor effects were evaluated through cell viability assays after 24 and 48 h of exposure, with additional cytotoxicity tests on HUVEC cells. Results: Results indicated that Melissa officinalis-derived silver nanoparticles (ME AgNPs) and Clematis vitalba extract with silver nanoparticles (CVE AgNPs) significantly reduced HepG2 cell viability. Their efficacy improved when combined with conventional therapies (SNTB + ME AgNPs 1:1 vs. SNTB: 20.01% vs. 25.73%, p = 0.002; IMTB + ME AgNPs 1:1 vs. IMTB: 17.80% vs. 18.08%, p = 0.036; SNTB + CVE AgNPs 1:1 vs. SNTB: 18.73% vs. 25.73%, p = 0.000; SNTB + CVE AgNPs 1:2 vs. SNTB: 26.62% vs. 41.00%, p = 0.018; IMTB + CVE AgNPs 1:1 vs. IMTB: 12.99% vs. 18.08%, p = 0.001). Taraxacum extract exhibited similar cytotoxicity to its nanoparticle formulation but did not exceed the efficacy of the extract alone at 24 h. Selectivity index assessments confirmed that AgNPs-based formulations significantly improve cytotoxicity and selectivity to HepG2 cells. Among the tested extracts, CVE demonstrated the strongest antitumor effect, enhancing the efficacy of synthetic drugs (CI < 1). SNTB + TE AgNPs (5% EtOH) also demonstrated consistent synergy at high doses, while SNTB + CVE AgNPs provided broad-range synergy, making it suitable for dose-escalation strategies. Conclusions: These findings underscore the potential of nanoparticle-based formulations in combination therapies with targeted kinase inhibitors such as sunitinib and imatinib. Future research should focus on in vivo validation and clinical trials to confirm these findings. Full article
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<p>(<b>I</b>). (a) Color change in the solution from brownish-red to a dark brown due to silver bioreduction by <span class="html-italic">Melissa officinalis</span> extract; (b) UV–Vis spectra of ME AgNPs samples obtained by reduction in time with <span class="html-italic">Melissa officinalis</span> extract; (c) UV–Vis spectra of 0.5 mM AgNO<sub>3</sub> aqueous solution; (<b>II</b>). (a) Color change in the solution from brownish-red to a dark brown due to silver bioreduction by <span class="html-italic">Clematis vitalba</span> extract; (b) UV–Vis spectra of CVE AgNPs samples obtained by reduction in time with <span class="html-italic">Clematis vitalba</span> extract. ME AgNPs: <span class="html-italic">Melissae extractum</span> silver nanoparticles; CVE AgNPs: <span class="html-italic">Clematis vitalbae extractum</span> silver nanoparticles.</p>
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<p>(<b>a</b>) DLS measurements of ME AgNPs; (<b>b</b>) SEM (Scanning Electron Microscopy) images of ME AgNPs; (<b>c</b>) Zeta potential of ME AgNPs, with a value of −12.29 mV. ME AgNPs: <span class="html-italic">Melissae extractum</span> silver nanoparticles.</p>
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<p>Cell viability (%) of HepG2 lines after: (<b>a</b>) 24 h of treatment with various dilutions of <span class="html-italic">Taraxaci extractum</span>-based samples and the chemotherapeutic drugs sunitinib and imatinib; (<b>b</b>) 48 h of treatment with various dilutions of <span class="html-italic">Taraxaci extractum</span>-based samples and the chemotherapeutic drugs sunitinib and imatinib. Error bars represent standard deviation (<span class="html-italic">n</span> = 3). The abbreviations are explained in <a href="#biomedicines-13-00641-t001" class="html-table">Table 1</a> and <a href="#biomedicines-13-00641-t004" class="html-table">Table 4</a>. Different colors represent various dilution ratios (v:v) for each sample with deionized water.</p>
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<p>Cell viability (%) of HepG2 lines after: (<b>a</b>) 24 h of treatment with various dilutions of <span class="html-italic">Melissae extractum</span>-based samples and the chemotherapeutic drugs sunitinib and imatinib; (<b>b</b>) 48 h of treatment with various dilutions of <span class="html-italic">Melissae extractum</span>-based samples and the chemotherapeutic drugs sunitinib and imatinib. Error bars represent standard deviation (<span class="html-italic">n</span> = 3). The abbreviations are explained in <a href="#biomedicines-13-00641-t002" class="html-table">Table 2</a> and <a href="#biomedicines-13-00641-t004" class="html-table">Table 4</a>. Different colors represent various dilution ratios (v:v) for each sample with deionized water.</p>
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<p>Cell viability (%) after: (<b>a</b>) 24 h of treatment of HepG2 and HUVEC by <span class="html-italic">Clematis vitalbae extractum</span>-based samples; (<b>b</b>) 48 h of treatment of HepG2 and HUVEC by <span class="html-italic">Clematis vitalbae extractum</span>-based samples. Error bars represent standard deviation (<span class="html-italic">n</span> = 3). The abbreviations are explained in <a href="#biomedicines-13-00641-t003" class="html-table">Table 3</a> and <a href="#biomedicines-13-00641-t004" class="html-table">Table 4</a>. Different colors represent various dilution ratios (v:v) for each sample with deionized water.</p>
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<p>Shaped matrix diagram to compare treatment groups using the intensity of the antitumor effect as a criterion. The abbreviations are explained in <a href="#biomedicines-13-00641-t001" class="html-table">Table 1</a>, <a href="#biomedicines-13-00641-t002" class="html-table">Table 2</a>, <a href="#biomedicines-13-00641-t003" class="html-table">Table 3</a> and <a href="#biomedicines-13-00641-t004" class="html-table">Table 4</a>.</p>
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<p>The SI variation of the compounds at 24 h and 48 h; interpretation of SI values: SI &gt; 2: good selectivity (the compound is at least twice as toxic to cancer cells compared to normal cells); SI between 1 and 2: moderate selectivity; SI &lt; 1: poor selectivity (the compound affects both cancer and normal cells similarly).</p>
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<p>The relationship between the CI and Fa for: (<b>a</b>) IMTB combinations compounds at 24 h; (<b>b</b>) IMTB combinations compounds at 48 h; (<b>c</b>) SNTB combination compounds at 24 h; and (<b>d</b>) SNTB combination compounds at 48 h.</p>
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<p>Potential mechanisms of AgNPs in cancer therapy: AgNPs induce apoptosis via the mitochondrial pathway by promoting cytochrome c release and caspase-3 activation. They also generate reactive oxygen species (ROS), causing oxidative stress and enhancing cell death. Additionally, AgNPs inhibit survival pathways, including PI3K/AKT and PDGFR, and disrupt angiogenesis through VEGFR inhibition, especially when combined with SNTB. Cell cycle arrest is induced at both G1/G2 and G2/M phases, inhibiting tumor proliferation. The combination of green-synthesized AgNPs with other agents exhibits synergistic effects, enhancing apoptosis, increasing ROS levels, and promoting antiangiogenic activity.</p>
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20 pages, 6127 KiB  
Article
Purification of Spent Hop Cone (Humulus lupulus L.) Extract with Xanthohumol Using Mesoporous Superparamagnetic Iron Oxide Nanoparticles
by Natalia Żuk, Sylwia Pasieczna-Patkowska, Ewelina Grabias-Blicharz, Magdalena Pizoń and Jolanta Flieger
Antioxidants 2025, 14(3), 314; https://doi.org/10.3390/antiox14030314 - 5 Mar 2025
Viewed by 226
Abstract
(1) Background: Over 90% of hop crops are currently used in beer production, with a small part used in the cosmetics and pharmaceutical industries. Spent hops as a waste product contain one of the strongest antioxidants, xanthohumol. The aim of the study was [...] Read more.
(1) Background: Over 90% of hop crops are currently used in beer production, with a small part used in the cosmetics and pharmaceutical industries. Spent hops as a waste product contain one of the strongest antioxidants, xanthohumol. The aim of the study was to purify spent hop extracts by magnetic dispersive extraction using iron oxide nanoparticles (IONP) to obtain pure xanthohumol; (2) Methods: The extract from the waste product obtained after supercritical carbon dioxide extraction of hops was prepared by ultrasound-assisted extraction utilizing different solvents, i.e., ethyl acetate, propanol, acetone, 80% methanol, ethyl acetate-methanol (1:1, v/v), and propanol-methanol (1:1, v/v). The hydrodynamic diameters and zeta potential of IONPs before and after incubation were measured by dynamic light scattering (DLS). The extracts were analyzed by reversed-phase high-performance liquid chromatography (HPLC). Isolated xanthohumol was identified based on the DAD spectrum in the range of 200–600 nm and by Fourier transform infrared spectroscopy/attenuated total reflectance (FT-IR/ATR); The antioxidant activity of extracts before and after incubation with IONPs was assessed using SNPAC (Silver Nanoparticle Antioxidant Capacity), DPPH (2,2-diphenyl-1-picrylhydrazyl radical), and FRAP (Ferric Reducing Antioxidant Power) assays, as well as total phenolic content (TPC) and total flavonoid content (TFC). (3) Results: The amount of added IONPs, the kind of solvent, and the contact time of the extract with nanoparticles were optimized. We found that 80% MeOH extract after incubation with IONPs (865 µg IONPs/g of spent hops) at room temperature for 48 h contains 74.61% of initial xanthohumol content, providing a final xanthohumol concentration of 43 µg mL−1. (4) Conclusions: The proposed method of magnetic dispersive extraction using IONPs allows for the purification of spent hops extract and obtaining a pure product, namely xanthohumol, with a wide potential for practical applications in medicine, pharmacy, cosmetics, and agriculture. This is clear evidence of the usefulness of IONP as an effective sorbent. The method allows the use of residues from the brewing industry, i.e., the biomass of used hop cones to obtain a valuable substance. Full article
(This article belongs to the Special Issue Green Extraction of Antioxidant from Natural Source)
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<p>The 3D chromatogram of 80% methanol extract of spent hops.</p>
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<p>Chromatogram of 80% methanol extract of spent hop cones after 48 h of contact with 750 mg IONPs added, with insert representing the overlaid spectra of recorded peak (blue line) and xanthohumol standard (red line) (<b>a</b>); 2D chromatogram representing the relationship of time versus wavelength (<b>b</b>).</p>
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<p>Overlaid chromatogram of acetone extract of spent hops (3 mL) with 100 mg IONPs recorded after 1 h, 2 h, 3 h, 4 h, and 5 h (from the top to the bottom).</p>
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<p>Chromatograms recorded after 5 h after mixing 1 mL of acetone extract of spent hops and 20, 40, 60, 80, 100, 110, and 130 mg of IONPs (from top to bottom).</p>
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<p>The 3D chromatograms of ethyl acetate-methanol extract (<b>a</b>) and extract recorded 3 h after mixing 1 mL of ethyl acetate-methanol extract of spent hops and 85 mg of IONPs (<b>b</b>).</p>
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<p>The FT-IR/ATR spectra of the purified extracts prepared in 80% methanol (<b>a</b>), ethyl acetate (<b>b</b>), acetone (<b>c</b>), propanol (<b>d</b>), and 1:1 mixtures of methanol-propanol (<b>e</b>) and methanol-ethyl acetate (<b>f</b>) compared to the xanthohumol standard.</p>
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<p>DLS measurement for synthesized IONPs before (red line) and after purification of spent hops extracted using different solvent systems: 80% methanol (blue line), ethyl acetate (brown line), acetone (green line), propanol (black line), 1:1, <span class="html-italic">v</span>/<span class="html-italic">v</span> ethyl acetate-methanol (pink line), 1:1, <span class="html-italic">v</span>/<span class="html-italic">v</span> propanol-methanol (deep violet line).</p>
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<p>Zeta potential measurement for synthesized IONPs before (red line) and after purification of spent hops extracts. The colors of the lines are the following: 80% methanol (green line), ethyl acetate (deep violet line), acetone (blue line), propanol (black line), 1:1, <span class="html-italic">v</span>/<span class="html-italic">v</span> ethyl acetate-methanol (brown line), 1:1, <span class="html-italic">v</span>/<span class="html-italic">v</span> propanol-methanol (pink line).</p>
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<p>Conductivity changes (µS) of IONP suspension prepared in different solvent systems at optimized concentration (<a href="#antioxidants-14-00314-t001" class="html-table">Table 1</a> and <a href="#antioxidants-14-00314-t002" class="html-table">Table 2</a>) as a function of time (h).</p>
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13 pages, 6924 KiB  
Article
Evaluation of Nano-Niclosamide in Killing Demodex folliculorum In Vitro and the Potential Application in Ocular Surface
by Jiani Li, Panqin Ma, Shujia Guo, Danyi Qin, Yuqian Wang, Yuwen Liu, Zixuan Yang, Caihong Huang, Yi Han and Zuguo Liu
Pharmaceutics 2025, 17(3), 332; https://doi.org/10.3390/pharmaceutics17030332 - 4 Mar 2025
Viewed by 282
Abstract
Background/Objectives: Blepharitis is a condition often caused by Demodex folliculorum infestations, resulting in significant ocular discomfort and surface damage. Current treatments offer only temporary relief and fail to eliminate mites effectively. This study evaluates nano-niclosamide (nano-NCL), a lipophilic nanosuspension designed to enhance solubility [...] Read more.
Background/Objectives: Blepharitis is a condition often caused by Demodex folliculorum infestations, resulting in significant ocular discomfort and surface damage. Current treatments offer only temporary relief and fail to eliminate mites effectively. This study evaluates nano-niclosamide (nano-NCL), a lipophilic nanosuspension designed to enhance solubility and permeability, for targeting Demodex folliculorum. Methods: Nano-NCL was characterized by particle size, zeta potential, transmission electron microscopy, pH measurement, bacterial culture, and HPLC. Viable Demodex mites were collected from patients’ eyelashes and assigned to six treatment groups: DDW, F127, 0.15% nano-NCL, 0.3% nano-NCL, 20% TTO, and Okra. Mite survival was analyzed using Kaplan–Meier curves. The ocular surface safety was assessed via slit-lamp examination, corneal fluorescein staining, and in vivo confocal microscopy. Results: The nano-NCL particles are uniformly rod-shaped, approximately 291 nm in size, and exhibit good stability, remaining suspended in various media for up to 20 days. The formulation has a stable pH of 6 and demonstrated no bacterial growth, indicating sterility and suitability for clinical use. In vitro, both 0.15% (w/v) and 0.30% (w/v) nano-NCL significantly reduced Demodex survival, with mortality rates ranging from 70.6% to 92.3% within 2 h. Safety evaluations showed minimal corneal staining and inflammation. Notably, 0.15% nano-NCL displayed efficacy comparable to that of 20% tea tree oil (TTO) and Okra, which are established anti-Demodex treatments. Conclusions: Nano-NCL, particularly at 0.15%, rapidly eliminates mites while maintaining excellent ocular tolerability, making it a promising treatment for Demodex-related ocular surface diseases. Full article
(This article belongs to the Special Issue Nanoparticles for Local Drug Delivery)
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<p>Preparation of nano-NCL. The preparation process primarily involves five steps, as indicated by the arrows: dissolution in ethanol, evaporation, hydration, sonication, and centrifugation. Specifically, NCL and Pluronic F127 were dissolved in ethanol and heated to evaporate the ethanol, and the resulting solid was dispersed in distilled water. After sonication and further treatment in an ice-water bath, the suspension was centrifuged, and the supernatant was collected as the nano-NCL product.</p>
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<p>Characterization of nano-NCL. (<b>A</b>) Transmission electron microscopy images of niclosamide (left) and nano-NCL (right). Scale bar: 100 nm. (<b>B</b>) Particle size distribution of nano-NCL. (<b>C</b>) Zeta potential of nano-NCL. (<b>D</b>–<b>F</b>) Particle size distribution of nano-NCL in DDW, PBS, and DMEM over time (0–20 d).</p>
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<p>Quality parameter evaluation. (<b>A</b>) Images of the nano-NCL solution. From left to right: 0.3% NCL in DDW, 0.15% nano-NCL, 0.3% nano-NCL, and 0.3% nano-NCL stored at room temperature for 3 weeks. (<b>B</b>) pH of nano-NCL over time. (<b>C</b>) Bacterial culture on LB agar plate: <span class="html-italic">E. coli</span> (left) and nano-NCL (right). (<b>D</b>) pH test paper detection of nano-NCL.</p>
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<p>(<b>A</b>) The general optical microscope images under 200× magnification of <span class="html-italic">Demodex folliculorum</span> in F127, 0.15% nano-NCL, and 0.30% nano-NCL. Scale bar: 100 µm. (<b>B</b>) Survival time (min) of <span class="html-italic">Demodex folliculorum</span> in the nano-NCL, Okra, and TTO groups. A one-way ANOVA test is used for 0.15% nano-NCL and other groups. *** <span class="html-italic">p</span> &lt; 0.001, ns: not significant. (<b>C</b>) Kaplan-Meier survival curves of <span class="html-italic">Demodex folliculorum</span> under different treatment groups.</p>
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<p>Safety assessment of nano-NCL. (<b>A</b>) Representative images of fluorescein sodium staining in Ctrl, 0.15% nano-NCL, and 0.3% nano-NCL. Scale bar: 1 mm (<b>B</b>) In vivo confocal microscopy images from different layers of the cornea after 0.15% nano-NCL and 0.3% nano-NCL eye drops administration twice a day for 7 days. Scale bar: 1 µm.</p>
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24 pages, 23251 KiB  
Article
In Vitro Evaluation of the Safety and Antineoplastic Effects in Gastrointestinal Tumors of Nanostructured Lipid Carriers Loaded with Berberine
by Denitsa Stefanova, Yordan Yordanov, Radostina Bogdanova, Christina Voycheva, Borislav Tzankov, Teodora Popova, Magdalena Kondeva-Burdina, Virginia Tzankova, Natalia Toncheva-Moncheva, Diana Tzankova and Marta Slavkova
Pharmaceutics 2025, 17(3), 331; https://doi.org/10.3390/pharmaceutics17030331 - 4 Mar 2025
Viewed by 219
Abstract
Background/Objectives: Natural substances have been a widely studied source of both pharmaceutical excipients and drugs. Berberine (BRB) is a benzylisoquinoline alkaloid isolated from different plant sources. It possesses various pharmacological properties including antibacterial, antitumor, antidiabetic, neuroprotective, hepatoprotective, anti-inflammatory, antioxidant, etc. However, the [...] Read more.
Background/Objectives: Natural substances have been a widely studied source of both pharmaceutical excipients and drugs. Berberine (BRB) is a benzylisoquinoline alkaloid isolated from different plant sources. It possesses various pharmacological properties including antibacterial, antitumor, antidiabetic, neuroprotective, hepatoprotective, anti-inflammatory, antioxidant, etc. However, the limited aqueous solubility hinders its application. Nanosized drug delivery systems are an innovative approach for addressing various challenges regarding drug delivery via different routes of administration. Their utilization could improve the solubility of active constituents. Methods: A melt-emulsification and ultrasonication technique was applied for the preparation of nanostructured lipid carriers (NLCs). They were thoroughly physicochemically characterized by the means of Dynamic Light Scattering, TEM, FTIR, DSC, TGA, and In Vitro release. The In Vitro efficacy and safety were evaluated on cholangiocarcinoma, colorectal adenocarcinoma, hepatocellular carcinoma, lymphoma, fibroblast, and cardioblast cells, as well as rat liver microsomes by means of cytotoxicity assays and the comet assay. Results: The obtained nanoparticles had a spherical shape and size around 158.2 ± 1.8 nm with negative zeta potential. They revealed successful drug loading and improved dissolution of berberine in physiological conditions. The In Vitro safety studies showed that loading BRB in NLCs resulted in improved or retained cytotoxicity to tumor cell lines and reduced cytotoxicity to normal cell lines and liver microsomes. The NLC itself increased microsomal malondialdehyde (MDA) and comet formation. Conclusions: A successful preparation of NLCs with berberine is presented. The nanocarriers show favorable physicochemical and biopharmaceutical properties. The cellular experiments show that the NLC loading of berberine could improve its anticancer efficacy and safety. These findings highlight the potential applicability of berberine in gastrointestinal neoplasms and build the foundation for future practical translation. Full article
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<p>Schematic illustration of the nanoparticle preparation.</p>
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<p>Transmission electron microscopy images of empty NLC (<b>A</b>) and BRB-loaded (NLC-B) nanoparticles (<b>B</b>) at 50 k magnification.</p>
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<p>FTIR spectra of the initial components, empty NLC, and berberine-loaded NLC-B (Myg—Mygliol<sup>®</sup> 812N; Prec—Precirol<sup>®</sup> 5 ATO).</p>
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<p>DSC thermograms of Precirol<sup>®</sup> 5 ATO, berberine, physical mixture (PM), physical mixture with berberine (PMB), empty (NLC), and berberine (NLC-B)-loaded nanoparticles.</p>
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<p>Release profile of free BRB and NLC-B in PBS with pH = 7.4 (mean ± SD; n = 3).</p>
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<p>In Vitro evaluation of the cytotoxicity of (<b>A</b>) empty NLC (1, 10, 50, 100, 250, 500, 1000, 2000 µg/mL), (<b>B</b>) BRB, and (<b>C</b>) NLC-B (0.1, 1, 5, 10, 25, 50, 100, 200 µM) on CaCo-2, 72 h after treatment, by means of MTT assay; * <span class="html-italic">p</span> &lt; 0.05, *** <span class="html-italic">p</span> &lt; 0.001. Statistical analysis was performed using ANOVA with a post-test of Dunnett. Values are presented as percentages of untreated cells and expressed as average values ± SEM (n = 6).</p>
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<p>In Vitro evaluation of the cytotoxicity of (<b>A</b>) empty NLC (1, 10, 50, 100, 250, 500, 1000, 2000 µg/mL), (<b>B</b>) BRB, and (<b>C</b>) NLC-B (0.1, 1, 5, 10, 25, 50, 100, 200 µM) on HuCC-T1 72 h after treatment, by means of MTT assay; * <span class="html-italic">p</span> &lt; 0.05, *** <span class="html-italic">p</span> &lt; 0.001. Statistical analysis was performed using ANOVA with a post-test of Dunnett. Values are presented as percentage of untreated cells and expressed as average values ± SEM (n = 6).</p>
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<p>In Vitro evaluation of the cytotoxicity of empty (<b>A</b>) NLC (1, 10, 50, 100, 250, 500, 1000, 2000 µg/mL), (<b>B</b>) BRB, and (<b>C</b>) NLC-B (0.1, 1, 5, 10, 25, 50, 100, 200 µM) on L929 24 h after treatment, by means of MTT assay; * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &gt; 0.001. Statistical analysis was performed using ANOVA with a post-test of Dunnett. Values are presented as percentage of untreated cells and expressed as average values ± SD (n = 6).</p>
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<p>In Vitro evaluation of the cytotoxicity of empty (<b>A</b>) NLC (1, 10, 50, 100, 250, 500, 1000, 2000 µg/mL), (<b>B</b>) BRB, and (<b>C</b>) NLC-B (0.1, 1, 5, 10, 25, 50, 100, 200 µM) on H9c2 cells 24 h after treatment, by means of MTT assay; * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &gt; 0.001. Statistical analysis was performed using ANOVA with a post-test of Dunnett. Values are presented as percentage of untreated cells and expressed as average values ± SEM (n = 6).</p>
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<p>Cell viability of L5178y cells, treated with NLC at 175, 350 and 700 µg/mL, normalized vs. controls (CTRL). Mean ± SD. *** <span class="html-italic">p</span> &lt; 0.001, one-way ANOVA with Dunnet’s post-test.</p>
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<p>Representative fluorescent micrographs of L5178y cells, treated with NLC (<b>C</b>), negative (<b>A</b>) or positive (<b>B</b>) control after being subjected to gel electrophoresis and stained with sybr green.</p>
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<p>Olive moments of L5178y cells, subjected to the comet assay after treatment with NLC at 350 µg/mL, negative (CTRL) or positive (H<sub>2</sub>O<sub>2</sub>) controls. Mean ± SD; *** <span class="html-italic">p</span> &lt; 0.001 vs. CTRL. Kruskal–Wallis test with Dun’s post-test.</p>
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<p>Effects of NLC, BRB, and NLC-B on MDA production in isolated rat liver microsomes. Data are presented as means from three independent experiments ± SD (n = 3). * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01. *** <span class="html-italic">p</span> &lt; 0.001 vs. control (non-treated microsomes).</p>
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15 pages, 6206 KiB  
Article
Surface-Modified Ceramic Boron Carbide as a Platform for Specific Targeting in Tumour Environments
by Dawid Kozień, Karolina Krygowska, Paulina Żeliszewska, Agnieszka Szczygieł, Anna Rudawska, Bożena Szermer-Olearnik, Piotr Rusiniak, Katarzyna Wątor, Katarzyna Węgierek-Ciura, Piotr Jeleń, Jakub Marchewka, Katarzyna Pasiut, Janusz Partyka, Elżbieta Pajtasz-Piasecka and Zbigniew Pędzich
Appl. Sci. 2025, 15(5), 2734; https://doi.org/10.3390/app15052734 - 4 Mar 2025
Viewed by 133
Abstract
Boron Neutron Capture Therapy (BNCT) is a therapeutic approach used to treat malignancies that are difficult to localise and typically inoperable. This therapy involves two stages: the administration of the boron (10B) isotope, which selectively enters cancer cells without affecting healthy [...] Read more.
Boron Neutron Capture Therapy (BNCT) is a therapeutic approach used to treat malignancies that are difficult to localise and typically inoperable. This therapy involves two stages: the administration of the boron (10B) isotope, which selectively enters cancer cells without affecting healthy tissue, followed by irradiation of the tumour with a neutron beam. In this study, boron carbide (B4C), a ceramic material with exceptional physical and chemical properties, was used as a nanoparticle platform for BNCT. The surface of the boron carbide nanoparticles was optimised by modifying them with compounds such as dextrin, dextran T70, sorbitol, lysine, and arginine. Boron carbide was synthesised directly from boron and carbon and then subjected to grinding, washing, and centrifugation. The unmodified and modified samples were analysed for their particle size, zeta potential, and toxicity against glioblastoma T98G cells. Additionally, FTIR spectroscopy confirmed the successful surface modifications. The results demonstrate that boron carbide, as a ceramic material, can be effectively functionalised with biocompatible compounds. Among the tested modifications, B4C-dextrin and B4C-dextran T70 exhibited the highest toxicity towards cancer cells, demonstrating the potential of ceramic platforms in biomedical applications. Full article
(This article belongs to the Special Issue Novel Ceramic Materials: Processes, Properties and Applications)
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<p>Dependence of the zeta potential of boron carbide on the concentration of (<b>a</b>) dextrin, (<b>b</b>) Dextran T50, (<b>c</b>) Dextran T70. The points denote experimental results obtained for pH 5.5, ionic strength 10<sup>−2</sup> M NaCl, and the B<sub>4</sub>C concentration of 100 mg L<sup>−1</sup>.</p>
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<p>Dependence of the zeta potential of boron carbide on the concentration of (<b>a</b>) sorbitol, (<b>b</b>) arginine, (<b>c</b>) lyzine. The points denote experimental results obtained for pH 5.5, ionic strength 10<sup>−2</sup> M NaCl, and the B<sub>4</sub>C concentration of 100 mg L<sup>−1</sup>.</p>
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<p>Dependence of hydrodynamic diameter of boron carbide on the concentration of (<b>a</b>) dextrin, (<b>b</b>) Dextran T50, (<b>c</b>) Dextran T70. The points denote experimental results obtained for pH 5.5, ionic strength 10<sup>−2</sup> M NaCl, and the B<sub>4</sub>C concentration of 100 mg L<sup>−1</sup>.</p>
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<p>Dependence of the hydrodynamic diameter of boron carbide on the concentration of (<b>a</b>) sorbitol, (<b>b</b>) arginine, (<b>c</b>) lyzine. The points denote experimental results obtained for pH 5.5, ionic strength 10<sup>−2</sup> M NaCl, and the B<sub>4</sub>C concentration of 100 mg L<sup>−1</sup>.</p>
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<p>FTIR spectra of selected samples—dextrin, lysin, B<sub>4</sub>C, and its modifications.</p>
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<p>Presents <sup>11</sup>B MAS-NMR spectra of B<sub>4</sub>C, its modifications and modifiers. As can be seen, the B<sub>4</sub>C exhibit typical signals at approximately 131, 81, and 2 ppms.</p>
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<p>Bioassay results: Viability of human glioblastoma multiforme cells treated with boron carbide and surface-modified boron carbide after 24, 48, and 72 h of incubation.</p>
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<p>Viability of glioblastoma multiforme cells treated with (<b>a</b>) pure B<sub>4</sub>C, (<b>b</b>) B<sub>4</sub>C functionalised with dextrin, (<b>c</b>) B<sub>4</sub>C functionalised with dextran T70, (<b>d</b>) B<sub>4</sub>C functionalised with sorbitol, (<b>e</b>) B<sub>4</sub>C functionalised with arginine, (<b>f</b>) B<sub>4</sub>C functionalised with lysine at different concentrations for 24, 48, and 72 h.</p>
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<p>Concentrations of B<sub>4</sub>C alone and functionalised B<sub>4</sub>C causing 50% inhibition of cell proliferation (IC50) calculated for T98G cell line: (<b>a</b>) pure B<sub>4</sub>C, (<b>b</b>) B<sub>4</sub>C functionalised with dextrin, (<b>c</b>) B<sub>4</sub>C functionalised with dextran T70, (<b>d</b>) B<sub>4</sub>C functionalised with sorbitol, (<b>e</b>) B<sub>4</sub>C functionalised with arginine, (<b>f</b>) B<sub>4</sub>C functionalised with lysine. Results are expressed as means + SD calculated for three independent experiments performed in triplicate. The abbreviation I.C. means “not possible to calculate”.</p>
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<p>TEM images of composites: (<b>a</b>) dextran ran T-70, (<b>b</b>) dextrin, (<b>c</b>) lysine (<b>d</b>) sorbitol, (<b>e</b>) boron glycol before modification.</p>
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