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Keywords = L2 oral development

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24 pages, 2391 KB  
Review
Watermelon Nutritional Composition with a Focus on L-Citrulline and Its Cardioprotective Health Effects—A Narrative Review
by Diego dos Santos Baião, Davi V. T. da Silva and Vania M. F. Paschoalin
Nutrients 2025, 17(20), 3221; https://doi.org/10.3390/nu17203221 - 14 Oct 2025
Viewed by 421
Abstract
Nitric oxide is a gaseous molecule endogenously produced by endothelial cells, which stands out for its vascular tone regulation effects after crossing through the endothelium and diffusing to smooth blood vessel muscle cells. Reduced nitric oxide bioavailability contributes to the development of hypertension, [...] Read more.
Nitric oxide is a gaseous molecule endogenously produced by endothelial cells, which stands out for its vascular tone regulation effects after crossing through the endothelium and diffusing to smooth blood vessel muscle cells. Reduced nitric oxide bioavailability contributes to the development of hypertension, atherosclerosis, worsening endothelial function, arterial stiffness, and ineffective stimulation of smooth muscle relaxation. L-citrulline, an amino acid found in high concentrations in watermelon, may serve as a recycling substrate, increasing L-arginine availability and, consequently, nitric oxide synthesis. By enhancing circulating L-arginine, L-citrulline indirectly improves the synthesis and bioavailability of nitric oxide, promoting smooth muscle vasodilation. Herein, this narrative review critically examines current evidence of the cardiovascular benefits of L-citrulline ingestion obtained exclusively through watermelon consumption, exploring the nutritional and bioactive composition of the edible parts of this fruit and the metabolism and effects of L-citrulline supplementation on vascular and metabolic physiology and proposing directions for future research, such as long-term studies and studies in specific populations. The beneficial effects of oral L-citrulline ingestion through watermelon require additional evidence, but it has already been demonstrated that it does not undergo hepatic metabolism, instead being transported to the kidneys to participate in de novo L-arginine synthesis. The generation of endogenous NO then causes positive biochemical, hemodynamic, and vascular effects, remodeling the physio-pathological conditions of those adults that present risk factors for cardiovascular diseases. Full article
(This article belongs to the Special Issue Benefits of Fruit Intake on Cardiovascular Health)
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16 pages, 887 KB  
Article
The Emerging Role of Magnesium in Preventing Acute Kidney Disease During Concurrent Chemoradiotherapy in Head and Neck Cancer
by Trevisani Francesco, Angioi Andrea, Floris Matteo, Cardellini Sara, Giordano Leone, Culiersi Alberta, Monti Agnese and Mirabile Aurora
Cancers 2025, 17(20), 3310; https://doi.org/10.3390/cancers17203310 - 14 Oct 2025
Viewed by 349
Abstract
Background: High-dose cisplatin (≥200 mg/m2 cumulative) remains the standard of care in concurrent chemoradiotherapy (CRT) for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). However, its use is frequently limited by nephrotoxicity, including acute kidney disease (AKD). This recently described clinical [...] Read more.
Background: High-dose cisplatin (≥200 mg/m2 cumulative) remains the standard of care in concurrent chemoradiotherapy (CRT) for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). However, its use is frequently limited by nephrotoxicity, including acute kidney disease (AKD). This recently described clinical renal syndrome encompasses functional alterations of the kidney lasting fewer than 3 months post-exposure. Although hydration protocols and antiemetic strategies are routinely applied to avoid reduction in oral liquid intake and to prevent dehydration that could worsen renal function, AKD continues to pose a threat to reach the therapeutic dose, to treatment completion, and long-term outcomes. Recent evidence supports the nephroprotective role of intravenous (IV) magnesium in mitigating cisplatin-induced tubular injury, yet prospective data on its impact in real-world LA-HNSCC settings remain limited. We aimed to prospectively investigate the incidence and characteristics of renal impairment, particularly AKD, in a real-world cohort of LA-HNSCC patients treated with high-dose cisplatin and standardized supportive therapy, including intravenous magnesium. Methods: We conducted a prospective observational study including 207 patients with LA- HNSCC undergoing high-dose cisplatin-based CRT (≥200 mg/m2 cumulative dose), within a standardized supportive care protocol incorporating IV magnesium. Renal function was assessed over three cycles via serum creatinine and estimated glomerular filtration rate (eGFR). AKD was defined and staged according to KDIGO criteria. Clinical and biochemical predictors of AKD were explored. Results: AKD occurred in 5.3% of patients (11/207; 95% CI 2.7–9.3), with eight events between C1→C2, 3 between C2→C3, and 0 thereafter; recovery at the next cycle was 9.1% (1/11). Among them, 57.1% were classified as stage 1. A baseline eGFR < 90 mL/min/1.73 m2 was associated with a higher AKD incidence (13.3% vs. 5.4%). Body mass index (BMI) was significantly associated with AKD in univariate analysis (p = 0.02), whereas no independent predictor emerged in multivariate analysis. Use of renin–angiotensin–aldosterone system (RAAS) inhibitors was more frequent among patients who developed AKD (p = 0.04). Renal function declined more steeply in AKD patients, with a median eGFR slope of −0.3917 mL/min/1.73 m2/day vs. −0.0483 mL/min/1.73 m2/day in those without AKD (p = 0.0005), irrespective of CKD stage. Conclusions: In a real-world cohort receiving high-dose cisplatin with structured nephroprotection including IV magnesium, AKD developed in approximately 10% of patients. Lower baseline eGFR, elevated BMI, and RAAS inhibitor use emerged as potential risk factors. These findings reinforce the importance of proactive renal monitoring and suggest a role for magnesium supplementation as an accessible strategy to enhance renal safety in curative-intent CRT. Full article
(This article belongs to the Section Clinical Research of Cancer)
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21 pages, 3438 KB  
Article
Research on Enhancing the Solubility and Bioavailability of Canagliflozin Using Spray Drying Techniques with a Quality-by-Design Approach
by Ji Ho Lee, Seong Uk Choi, Tae Jong Kim, Na Yoon Jeong, Hyun Seo Paeng and Kyeong Soo Kim
Pharmaceutics 2025, 17(10), 1319; https://doi.org/10.3390/pharmaceutics17101319 - 11 Oct 2025
Viewed by 303
Abstract
Objectives: The objective of this study was to enhance the solubility and bioavailability of canagliflozin (CFZ) using a spray drying technique with a Quality-by-Design (QbD) approach. Methods: The formulation of CFZ-loaded solid dispersions (CFZ-SDs) was optimized using a Box–Behnken design (BBD) [...] Read more.
Objectives: The objective of this study was to enhance the solubility and bioavailability of canagliflozin (CFZ) using a spray drying technique with a Quality-by-Design (QbD) approach. Methods: The formulation of CFZ-loaded solid dispersions (CFZ-SDs) was optimized using a Box–Behnken design (BBD) with three factors at three levels, resulting in a total of fifteen experiments, including three central point replicates. The design space was determined using the BBD, and the optimized CFZ-SD was evaluated for reproducibility, morphology, and physical properties and subjected to in vitro and in vivo tests. Results: The optimal values for each X factor were identified using a response optimization tool, achieving a yield (Y1) of 62.8%, a solubility (Y2) of 9941 μg/mL, and a particle size (Y3) of 5.89 μm, all of which were within the 95% prediction interval (PI). Additionally, amorphization induced by spray drying was confirmed for the optimized CFZ-SD using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) analyses. In in vitro dissolution tests, the final dissolution rate of the CFZ-SD increased 3.58-fold at pH 1.2 and 3.84-fold at pH 6.8 compared to an Invokana® tablet. In addition, relative to CFZ, it showed an 8.67-fold and 8.85-fold increase at pH 1.2 and pH 6.8, respectively. The in vivo pharmacokinetic behavior of CFZ and the CFZ-SD was evaluated in Sprague–Dawley rats following oral administration at a dose of 5 mg/kg. The AUC of the CFZ-SD increased 1.9-fold compared to that of CFZ. Conclusions: In this study, a solid dispersion (SD) formulation of CFZ, a BCS class IV SGLT2 inhibitor, was developed and optimized using a QbD approach to enhance solubility and oral bioavailability. Full article
(This article belongs to the Special Issue Methods of Potentially Improving Drug Permeation and Bioavailability)
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16 pages, 1083 KB  
Article
Simultaneous Development and Validation of an HPLC Method for the Determination of Furosemide and Its Degraded Compound in Pediatric Extemporaneous Furosemide Oral Solution
by Katsanee Srejomthong, Thanawat Pattananandecha, Sutasinee Apichai, Suporn Charumanee, Busaban Sirithunyalug, Fumihiko Ogata, Naohito Kawasaki and Chalermpong Saenjum
Molecules 2025, 30(19), 4031; https://doi.org/10.3390/molecules30194031 - 9 Oct 2025
Viewed by 366
Abstract
Furosemide (FUR) is a loop diuretic widely used in pediatric care. However, no standardized oral liquid formulation exists due to degradation concerns, particularly the formation of furosemide-related compound B (FUR-B). This study aimed to develop and validate the HPLC method for the simultaneous [...] Read more.
Furosemide (FUR) is a loop diuretic widely used in pediatric care. However, no standardized oral liquid formulation exists due to degradation concerns, particularly the formation of furosemide-related compound B (FUR-B). This study aimed to develop and validate the HPLC method for the simultaneous quantification of FUR, FUR-B, methylparaben (MP), and propylparaben (PP) in pediatric extemporaneous oral solutions. Chromatographic separation was achieved using a Symmetry® C18 column (4.6 × 250 mm, 5 µm) with a mobile phase of 0.1% acetic acid in water and acetonitrile (60:40, v/v) at 1.0 mL/min of flow with injection volume at 10 µL. Detection at 272 nm provided optimal sensitivity, especially for low concentrations of FUR-B. Forced degradation confirmed baseline separation of FUR from its degradation products. The condition showed high linearity (R2 > 0.995), accuracy (recoveries 98.2–101.0%), and precision (RSD ≤ 2%). Robustness and ruggedness tests under varied conditions, analysts, and intra-day yielded consistent performance. Application to extemporaneous formulations showed that refrigeration (2–8 °C) retained initial composition, while elevated temperatures (30 °C and 40 °C) promoted FUR degradation, with FUR-B increasing to 6.84% after 90 days and greater MP and PP degradation. This validated method offers a reliable analytical tool for monitoring chemical changes and supporting quality control of pediatric FUR extemporaneous formulations. Full article
(This article belongs to the Special Issue Recent Advances in Chromatography for Pharmaceutical Analysis)
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16 pages, 1105 KB  
Article
Chronic Kidney Disease and Oral Health: A Cross-Sectional Study
by Michele Basilicata, Manuela Di Lauro, Giovanni Bruno, Kevin Cornali, Giulia Marrone, Claudia Masci, Giuseppe Troiano, Simone Manca di Villahermosa, Anna Paola Mitterhofer, Patrizio Bollero and Annalisa Noce
Appl. Sci. 2025, 15(19), 10804; https://doi.org/10.3390/app151910804 - 8 Oct 2025
Viewed by 441
Abstract
Objective: This pilot study investigated the association between chronic kidney disease (CKD) and oral health, focusing on the prevalence and severity of periodontal disease (PD) in the different CKD stages. Moreover, we explored how systemic alterations related to kidney dysfunction may influence oral [...] Read more.
Objective: This pilot study investigated the association between chronic kidney disease (CKD) and oral health, focusing on the prevalence and severity of periodontal disease (PD) in the different CKD stages. Moreover, we explored how systemic alterations related to kidney dysfunction may influence oral conditions. Methods: A cross-sectional observational study was conducted on seventy-five adult CKD patients (stages G1–G5) under conservative therapy. Participants underwent clinical, biochemical, and dental assessments. Periodontal parameters, such as the plaque index, bleeding on probing, clinical attachment loss, and gingival recession, were evaluated. Results: A significant inverse relationship was found between the estimated glomerular filtration rate (e-GFR) and PD severity, plaque index, and gingival inflammation. Advanced CKD patients exhibited a higher prevalence of generalized gingivitis and more severe PD stages and grades. Patients with e-GFR below 44 mL/min/1.73 m2 had a 3.3-fold higher risk of developing PD. In our population, the prevalence of xerostomia and dysgeusia was 45% and 15%, respectively, with taste alteration correlating directly with declining kidney function. Conclusions: CKD patients demonstrate compromised oral health, with an increased risk of PD. Renal dysfunction appears to be a significant factor influencing the onset and progression of PD. Further studies are necessary to clarify the underlying mechanisms and to develop integrated management strategies. Full article
(This article belongs to the Section Applied Dentistry and Oral Sciences)
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17 pages, 4833 KB  
Article
Lactoferrin-Loaded Liposomal Nanoparticles: Enhanced Intestinal Stability and Bioactivity for Mitigating Radiation-Induced Intestinal Injury
by Yingying Lin, Rui Ding, Yuning Zhang, Yimeng Wang, Sijia Song and Huiyuan Guo
Foods 2025, 14(19), 3410; https://doi.org/10.3390/foods14193410 - 2 Oct 2025
Viewed by 476
Abstract
Radiation-induced intestinal injury (RIII), a severe complication of abdominopelvic radiotherapy, causes intestinal ischemia, ulcers, and necrosis, severely impacting patients’ quality of life. Currently, effective treatments are limited, and a specific cure remains elusive. Our previous research showed that lactoferrin (LF) can promote intestinal [...] Read more.
Radiation-induced intestinal injury (RIII), a severe complication of abdominopelvic radiotherapy, causes intestinal ischemia, ulcers, and necrosis, severely impacting patients’ quality of life. Currently, effective treatments are limited, and a specific cure remains elusive. Our previous research showed that lactoferrin (LF) can promote intestinal stem cell (ISC) proliferation and tissue repair; however, its oral administration is limited by rapid degradation in the gastric environment. In this study, we developed LF-loaded liposomal nanoparticles (Lip-LF) using a simple ethanol injection method. The optimal formulation (cholesterol/egg yolk lecithin ratio 2:8, LF concentration 12.5 mg/mL) achieved a drug-loading capacity of 6.8% and a narrow size distribution (0.2 < PDI < 0.4). In vitro experiments demonstrated that Lip-LF protected LF from pepsin degradation in simulated gastric fluid (SGF), retaining over 80% integrity after 120 min, while releasing in simulated intestinal fluid (SIF). In vivo imaging revealed prolonged gastrointestinal retention of Lip-LF compared to free LF. In a murine model of RIII (12 Gy whole-body irradiation), Lip-LF significantly restored villus counts, increased crypt height, and promoted goblet-cell regeneration. Immunohistochemical and qPCR analyses revealed enhanced ISCs proliferation and upregulation of repair-associated genes, including Pcna and Olfm4. These findings demonstrate that Lip-LF protects LF from gastric degradation and enhances its targeted delivery to the intestine, improving its therapeutic efficacy in repairing RIII. Lip-LF thus offers a promising strategy for managing RIII. Full article
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22 pages, 1386 KB  
Article
Pharmacokinetic Profile of Extracts from the Chayote (Sechium edule) H387 07 Hybrid and Phytochemical Characterization of Its Segregant H387 M16 for Potential Therapeutic Applications
by Eugenia Elisa Delgado-Tiburcio, Ramón Marcos Soto-Hernández, Itzen Aguiñiga-Sánchez, Jorge Cadena-Iñiguez, Lucero del Mar Ruiz-Posadas, Cecilia B. Peña-Valdivia and Héctor Gómez-Yáñez
Molecules 2025, 30(19), 3948; https://doi.org/10.3390/molecules30193948 - 1 Oct 2025
Viewed by 457
Abstract
The hybrid Sechium edule H387 07, commonly known as chayote, has shown potential as an antiproliferative, cytotoxic, and pro-apoptotic agent in the murine leukemia cell lines P388 (macrophagic) and J774 (monocytic) and in the myelomonocytic leukemia cell line WEHI-3. However, despite these reported [...] Read more.
The hybrid Sechium edule H387 07, commonly known as chayote, has shown potential as an antiproliferative, cytotoxic, and pro-apoptotic agent in the murine leukemia cell lines P388 (macrophagic) and J774 (monocytic) and in the myelomonocytic leukemia cell line WEHI-3. However, despite these reported bioactivities, its pharmacokinetic profile remains largely unexplored. Understanding the absorption, distribution, and elimination of this hybrid is critical for addressing unmet therapeutic needs and for advancing the development of natural product-based therapies. These effects are attributed to the presence of phenols, flavonoids, and cucurbitacins in its organic extracts. In this study, the pharmacokinetic parameters of secondary metabolites from methanolic extracts of Sechium H387 07 were evaluated after oral administration in mice, while its segregant H387 M16 was subjected to complementary phytochemical characterization. Methanolic extracts of Sechium edule H387 07 were orally administered to mice at doses of 8, 125, and 250 mg/kg, and plasma, liver, and urine samples were collected at 1, 6, 24, and 48 h post-treatment. High-performance liquid chromatography (HPLC) identified polyphenols and cucurbitacins, notably cucurbitacin B (CuB) and cucurbitacin IIA (CuIIA), in the biological samples, and pharmacokinetic variables such as the maximum plasma concentration (Cmax), time to reach maximum concentration (Tmax), half-life (T1/2), and volume of distribution (Vd) were determined. For instance, CuB exhibited a Cmax of 37.56 µg/mL at 1 h post-dose after oral administration of 125 mg/kg, confirming its rapid absorption and systemic distribution. Notably, the presence of CuIIA in plasma was documented for the first time, along with the pharmacokinetic profiles of apigenin, phloretin, CuB, CuE, and CuI. In parallel, the segregant H387 M16 was characterized via colorimetric assays, thin-layer chromatography (TLC), HPLC, and antioxidant activity tests, which revealed high levels of flavonoids, phenols, and cucurbitacins, with an antioxidant activity of approximately 75% at the highest tested dose (1 mg/mL), supporting its suitability for future bioassays. Overall, these findings not only provide novel pharmacokinetic data for key metabolites of the H387 07 hybrid but also establish the phytochemical and antioxidant profile of its segregant H387 M16. This dual characterization strengthens the evidence of the therapeutic potential of Sechium genotypes and provides a valuable foundation for future studies aiming to develop standardized protocols and explore translational applications in drug development and natural product-based therapies. Full article
(This article belongs to the Section Natural Products Chemistry)
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12 pages, 1339 KB  
Article
Antifungal and Cytocompatible Properties of Juglans regia Extract for Dental Applications: A Novel Approach Against Oral Candida Infections
by Diego Garcia Miranda, Lucas de Paula Ramos, Flavia Villaça Morais, Letícia Silva Nascimento, Isadora Abdalla Ferreira, Bruno Martini Guimarães, Fernanda Malagutti Tomé, Flavia Pires Rodrigues and Florence Carrouel
Appl. Sci. 2025, 15(19), 10531; https://doi.org/10.3390/app151910531 - 29 Sep 2025
Viewed by 327
Abstract
Oral Candida infections result from the overgrowth of this opportunistic fungus in the oral mucosa. Risk factors include immunosuppression, antibiotic or corticosteroid use, xerostomia, and conditions such as diabetes mellitus. Fungal resistance in Candida spp. has become a significant challenge, especially due to [...] Read more.
Oral Candida infections result from the overgrowth of this opportunistic fungus in the oral mucosa. Risk factors include immunosuppression, antibiotic or corticosteroid use, xerostomia, and conditions such as diabetes mellitus. Fungal resistance in Candida spp. has become a significant challenge, especially due to the excessive use of conventional antifungals such as azoles, echinocandins, and polyenes. Therefore, this study aims to determine the spectrum of antifungal activity of Juglans regia and assess its cytotoxicity on hepatocytes. Thus, a broth microdilution test was conducted according to the CLSI (M27-A3) guidelines. After initial screening, biofilm tests were conducted using the crystal violet (CV) and metabolic activity assays (MTT). Cytotoxicity was evaluated on human hepatocytes (HEPG2). The J. regia extract showed dose-dependent antifungal activity. At a concentration of 200 mg/mL, inhibition was greater according to the CV test in Candida albicans (31%) and Candida tropicalis (30.4%), while the MTT assay indicated a greater reduction in viability in C. albicans (61%) and C. glabrata (53.5%). At 100 mg/mL, C. albicans remained sensitive (37.7% CV; 71.6% MTT), while C. krusei and C. dubliniensis showed low viability by MTT (18.4% and 11.8%, respectively). At 50 mg/mL, C. albicans remained affected (74.3% MTT), but C. krusei, C. dubliniensis, and C. guilliermondii showed the lowest viability values (≤19.4% MTT), suggesting greater sensitivity to lower concentrations. These results indicate variation in susceptibility between species, with C. albicans being consistently inhibited, while C. krusei and C. dubliniensis responded better to lower doses. The extract showed cytocompatibility when applied to human hepatoma cells (HEPG2) and therefore holds significant potential for developing a new therapeutic approach. Full article
(This article belongs to the Special Issue Advanced Dental Materials and Its Applications)
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24 pages, 1991 KB  
Article
Third Languages Acquisition (TLA): Educational Multilingualism at Early Ages
by M.ª Dolores Asensio Ferreiro
Languages 2025, 10(10), 251; https://doi.org/10.3390/languages10100251 - 29 Sep 2025
Viewed by 489
Abstract
In an increasingly globalized world, learning foreign languages (FLs) is essential, particularly in education. Multilingualism is critical due to the multicultural and interconnected nature of societies, yet early third language acquisition (TLA) is not widely adopted in schools. This study investigates how the [...] Read more.
In an increasingly globalized world, learning foreign languages (FLs) is essential, particularly in education. Multilingualism is critical due to the multicultural and interconnected nature of societies, yet early third language acquisition (TLA) is not widely adopted in schools. This study investigates how the simultaneous learning of Spanish first language (L1), a second language (L2), and a third language (L3) impacts oral language (OL) development in L1 and whether prior L2 knowledge aids L3 acquisition. The study involved bilingual (L1 + L2) and trilingual (L1 + L2 + L3) learners. Data were collected using the Navarre Oral Language Test-Revised, which evaluates phonological, morphological–syntactic, lexical–semantic, and pragmatic competencies in oral communication. Findings revealed that trilingual learners showed better OL development in L1 compared to bilingual learners. Additionally, prior L2 knowledge facilitated L3 learning, highlighting the benefits of early trilingual education. The study demonstrates that early trilingual learning positively impacts OL development in L1. These results contribute significantly to research on TLA and the advancement of multilingual education. Full article
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27 pages, 4484 KB  
Article
Formulation of Self-Emulsifying Microemulsion for Acemetacin Using D-Optimal Design: Enteric-Coated Capsule for Targeted Intestinal Release and Bioavailability Enhancement
by Zaineb Z. Abduljaleel and Khalid K. Al-Kinani
Pharmaceutics 2025, 17(10), 1270; https://doi.org/10.3390/pharmaceutics17101270 - 27 Sep 2025
Viewed by 712
Abstract
Objectives: The current work aimed to formulate and optimize a self-emulsifying microemulsion drug delivery system (SEME) for acemetacin (ACM) to increase ACM’s aqueous solubility, improve oral bioavailability, and reduce gastrointestinal complications. Methods: Screening of components capable of enhancing ACM solubility was [...] Read more.
Objectives: The current work aimed to formulate and optimize a self-emulsifying microemulsion drug delivery system (SEME) for acemetacin (ACM) to increase ACM’s aqueous solubility, improve oral bioavailability, and reduce gastrointestinal complications. Methods: Screening of components capable of enhancing ACM solubility was performed. Pseudo-ternary phase diagrams were performed to choose the optimal formulation ratio. The ACM-SEME formulation’s composition was optimized using D-optimal design. Oil, Smix, and water percentages were used as independent variables, while globule size, polydispersity index, ACM content, and in vitro ACM release after 90 min were used as dependent variables. Also, thermodynamic stability and transmittance percentage tests were studied. Zeta potential was assessed for the optimized ACM-SEME formulation, which was then subjected to spray drying. The dried ACM-SEME was characterized using field-emission scanning electron microscope, Fourier-transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. The dried ACM-SEME formulation was filled into hard gelatin capsules and coated with Eudragit L100 to achieve pH-dependent release. Results: The antinociceptive activity of ACM-SEME was evaluated in vivo using Eddy’s hot plate test in rats, revealing a significant prolongation of the noxious time threshold compared to control groups. Ex vivo permeation studies across rat intestinal tissue confirmed the enhanced permeation potential of the ACM-SEME. Conclusions: It was concluded that the developed ACM-SEME system demonstrated improved physicochemical properties, enhanced release behavior, and superior therapeutic performance, highlighting its potential as a safer and more effective oral delivery platform for ACM. Full article
(This article belongs to the Special Issue Advances in Emulsifying Drug Delivery Systems)
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14 pages, 1254 KB  
Article
Antimicrobial Activity of Ethanolic Propolis Extracts from Tame (Arauca) on Oral Biofilm Co-Cultures
by Ana Isabel Moreno-Florez, Claudia Maria Bedoya-Correa, Claudia Garcia and Alejandro Pelaez-Vargas
Pathogens 2025, 14(10), 982; https://doi.org/10.3390/pathogens14100982 - 27 Sep 2025
Viewed by 521
Abstract
Oral diseases such as dental caries, stomatitis, and periodontitis are closely associated with biofilms that are resistant to conventional therapeutic approaches. Streptococcus sanguinis and Streptococcus mutans play a key role as primary and secondary colonizers of oral surfaces, respectively, and interact synergistically with [...] Read more.
Oral diseases such as dental caries, stomatitis, and periodontitis are closely associated with biofilms that are resistant to conventional therapeutic approaches. Streptococcus sanguinis and Streptococcus mutans play a key role as primary and secondary colonizers of oral surfaces, respectively, and interact synergistically with other species, including Candida albicans, to promote the establishment and progression of infection. Objective: To evaluate the antimicrobial activity of ethanolic extracts of propolis from Tame (Arauca) on biofilms formed in co-cultures from reference strains and co-cultures with clinical isolates of oral pathogens. Methodology: Propolis was collected from Apis mellifera hives placed in rural Tame (Arauca), located in the foothills of the Eastern Andes (Colombia). Ethanolic extracts of propolis (EEP) were prepared in a 0.07 g/mL concentration and biological characterization was performed on single and complex co-cultures of S. mutans (serotype c), S. sanguinis, and C. albicans using disc diffusion test, determination of MIC and BMC, growth curves and biofilm formation. The cell viability and metabolic activity of primary cell cultures derived from a dental pulp explant were evaluated using the MTT assay. Results: EEP exhibited higher inhibition zones than chlorhexidine against S. mutans and C. albicans and lower efficacy against S. sanguinis. Among the microorganisms evaluated, S. mutans showed the lowest MIC and BCM values, followed by C. albicans and S. sanguinis. Growth curves and biofilm formation assays revealed higher inhibition in co-cultures of reference strains (S. mutans + C. albicans), while multi-species cultures (S. mutans + S. sanguinis + C. albicans), or clinical strains (S. mutans clinical isolated + S. sanguinis + C. albicans), showed higher resistance. Cell viability assays revealed low cytotoxicity (<30%) in primary cell cultures. Conclusions: EEPs exhibited antimicrobial activity against relevant oral pathogens, especially in simple co-cultures, supporting their potential as natural therapeutic alternatives. However, their efficacy decreases in the presence of clinical strains and complex co-cultures, highlighting the importance of considering these variables in the development of oral treatments. Full article
(This article belongs to the Special Issue Candida albicans Virulence and Therapeutic Strategies)
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18 pages, 12913 KB  
Article
Effect of Cleaning Protocols on Surface Roughness of Current Polymeric Denture Materials
by Lisa Brinkmann, Florian Fuchs, Martin Rosentritt, Oliver Schierz, Andreas Koenig and Daniel R. Reissmann
J. Funct. Biomater. 2025, 16(10), 359; https://doi.org/10.3390/jfb16100359 - 24 Sep 2025
Viewed by 720
Abstract
Surface roughness influences biofilm adhesion on denture base materials, impacting oral health. Despite advances in polymeric denture materials, the effects of common cleaning protocols on their surface texture remain inadequately characterized. This study investigated the influence of toothbrush abrasion on the surface texture [...] Read more.
Surface roughness influences biofilm adhesion on denture base materials, impacting oral health. Despite advances in polymeric denture materials, the effects of common cleaning protocols on their surface texture remain inadequately characterized. This study investigated the influence of toothbrush abrasion on the surface texture of dimethyl methacrylate-based (DMA, printed: V-Print dentbase), polymethyl methacrylate (PMMA, milled: VITA Vionic Base, pressed: IvoBase Hybrid), polyamide (PA, pressed: Bre.flex), and polyether ether ketone (PEEK, milled: Juvora Disc). The specimens were fabricated as polished discs. The Vickers and Martens hardness, indentation modulus, elastic and plastic part of indentation work, and indentation creep were determined. Toothbrushing simulation and surface texture analysis were conducted in three steps: 1800, 1800, and 3600 cycles using water, dish detergent, or toothpaste slurry. The surface texture parameters Sa, Sal, Sdr, Sku, and Ssk were determined using confocal laser scanning microscopy and suitable filtering (S-F and S-L surface). Sa, Sal, and Sdr showed significant changes depending on the choice of medium and the material used. The duration had a small effect (three-way ANOVA; all p < 0.001). DMA showed minor surface changes. Milled and pressed PMMA exhibited similar surface deformities due to wide valleys that were not considered critical for biofilm adhesion. PA showed the lowest and PEEK the highest Vickers and Martens hardness. However, both PA and PEEK exhibited surface changes that could promote biofilm development. These findings suggest that denture cleaning recommendations should remain material-specific. Regular surface inspections and repolishing are necessary to reduce the risk of biofilm formation on PA or PEEK-containing dentures. Full article
(This article belongs to the Section Dental Biomaterials)
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15 pages, 1226 KB  
Article
Vitamin D Nanoliposomes to Improve Solubility, Stability, and Uptake Across Intestinal Barrier
by Cosimo Landi, Elisa Landucci, Costanza Mazzantini, Rebecca Castellacci and Maria Camilla Bergonzi
Pharmaceutics 2025, 17(10), 1244; https://doi.org/10.3390/pharmaceutics17101244 - 23 Sep 2025
Viewed by 393
Abstract
Background/Objectives: Vitamin D (VD) is a fat-soluble vitamin essential for bone health, and calcium and phosphorus absorption. Recently, new interesting functions are reported such as neuroprotective activity, regulatory roles in the immune system, and protective effects in cancer patients. However, the lipophilic [...] Read more.
Background/Objectives: Vitamin D (VD) is a fat-soluble vitamin essential for bone health, and calcium and phosphorus absorption. Recently, new interesting functions are reported such as neuroprotective activity, regulatory roles in the immune system, and protective effects in cancer patients. However, the lipophilic nature of VD represents a limitation, as it is associated with low solubility and poor absorption; additionally, VD exhibits poor stability. Methods: Two nanoliposomes containing VD, conventional (LP-VD) and conjugated with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS, LPT-VD), were developed. The physical and chemical stability during the storage and gastrointestinal stability, the dissolution profile, the cytotoxicity and the Caco-2 cellular uptake were investigated. Nanoliposomes were fully characterized determining sizes, PdI, Zeta potential, encapsulation efficiency and recovery and they were lyophilized to improve stability. Subsequently, the freeze-dried liposomes were encapsulated in hard gelatin capsules to mimic an oral dosage form, and they were subjected to dissolution test. Results: LP-VD exhibited an average size of 85.50 ± 5.70 nm, a PdI of 0.24 ± 0.06, and a ZP of −20.90 ± 4.37 mV. LPT-VD showed an average size of 61.70 ± 3.90 nm, a PdI of 0.26 ± 0.02, and a ZP of −9.45 ± 2.99 mV. The EE% values were 95.76 ± 1.26% and 97.54 ± 3.24% for LP-VD and LPT-VD, respectively. Both nanoliposomes solubilized 2 mg/mL of VD and improved both its storage stability and stability in aqueous and gastrointestinal environment. The freeze-dried products guarantee constant chemical-physical parameters for 28 days at 25 °C. VD dissolution profile was improved. Conclusions: Nanoliposomes, in particular LPT-VD, showed the best results in terms of chemical stability, dissolution profile, and Caco-2 cellular uptake, confirming the stabilization, bioenhancer properties and P-gp inhibition capabilities of TPGS. Full article
(This article belongs to the Special Issue Liposomes Applied in Drug Delivery Systems)
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18 pages, 1880 KB  
Article
Physiologically Based Pharmacokinetic Modelling of Serum 25-Hydroxyvitamin D Concentrations in Schoolchildren Receiving Weekly Oral Vitamin D3 Supplementation
by Nadda Muhamad, Neil Walker, Keren Middelkoop, Davaasambuu Ganmaa, Adrian R. Martineau and Tao You
Nutrients 2025, 17(19), 3028; https://doi.org/10.3390/nu17193028 - 23 Sep 2025
Viewed by 472
Abstract
Background: Following vitamin D3 oral administration, attained serum concentrations of its metabolite 25-hydroxyvitamin D3 (25(OH)D3) are variable among children. Methods: We developed physiologically based pharmacokinetic (PBPK) modelling using annually measured serum 25(OH)D3 concentrations in 77 Cape Town schoolchildren [...] Read more.
Background: Following vitamin D3 oral administration, attained serum concentrations of its metabolite 25-hydroxyvitamin D3 (25(OH)D3) are variable among children. Methods: We developed physiologically based pharmacokinetic (PBPK) modelling using annually measured serum 25(OH)D3 concentrations in 77 Cape Town schoolchildren aged 6–11 years who received weekly oral doses of 10,000 IU vitamin D3 for 3 years during a clinical trial (Δ25(OH)D = 32.2 nmol/L, 95% CI: [−3.2, 65.8] nmol/L). Simulations were performed to test the model on 463 other participants in the same trial, and in a cohort of 1756 Mongolian schoolchildren aged 6–11 years who received weekly oral doses of 14,000 IU vitamin D3 for 3 years in another trial. Results: The best model attributed most of the variability in post-supplementation 25(OH)D3 concentrations to hepatic clearance and covariates including weight (ΔAIC = −21) and ZBMI (body mass index Z-score, ΔAIC = −34). For 463 other children from the Cape Town trial (Δ25(OH)D = 25.8 nmol/L, 95% CI: [8.3, 47.2] nmol/L), mean estimation error was 5.3 nmol/L, and 76.7% of observations were within the 95% prediction intervals. Our simulation supported the previous proposal that serum 25(OH)D3 should exceed 50 nmol/L among 97.5% of European children at 24.4 μg/day vitamin D3 dosing. At a higher weekly dose (14,000 IU), the Mongolian children demonstrated a higher average increase in serum 25(OH)D3 (40.6 [−2.9, 88.9] nmol/L) but were overestimated by the model. Conclusion: We developed the first PBPK model to successfully predict the long-term serum 25(OH)D3 increases in healthy schoolchildren in Cape Town who received orally administered vitamin D3 and exhibited higher relative increases than Mongolian children. Full article
(This article belongs to the Section Pediatric Nutrition)
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20 pages, 7319 KB  
Article
Modification of Brassica rapa L. Polysaccharide by Selenylation and Its Immune-Enhancing Activity When Combined with a Live-Attenuated Newcastle Disease Vaccine in Poultry
by Sijia Wang, Jungang Wang and Hong Shen
Animals 2025, 15(18), 2755; https://doi.org/10.3390/ani15182755 - 21 Sep 2025
Viewed by 429
Abstract
Background: The quest for effective immunoenhancers is central to improving vaccine efficacy, especially against avian viruses such as Newcastle disease (ND) virus. Selenized polysaccharides integrate bioactive polysaccharides with selenium’s immunoenhancing properties while reducing selenium toxicity, making them promising candidates for the development [...] Read more.
Background: The quest for effective immunoenhancers is central to improving vaccine efficacy, especially against avian viruses such as Newcastle disease (ND) virus. Selenized polysaccharides integrate bioactive polysaccharides with selenium’s immunoenhancing properties while reducing selenium toxicity, making them promising candidates for the development of a novel vaccine immunoenhancer. Aim: This study aimed to develop an efficient selenized Brassica rapa L. polysaccharide (sBRP) and evaluate its potential to enhance the immunogenicity of a live-attenuated ND vaccine in poultry. Methods: Selenization was achieved via nitrite-assisted selenization of Brassica rapa L. polysaccharide (BRP). In vivo, 180 yellow-feathered broilers were divided into six groups: control (Con), vaccine-only (Vac), BRP (20 mg/kg), and low/medium/high-dose sBRP (sBRP-L/M/H: 5/10/20 mg/kg). On days 14 and 28, all groups except Con were vaccinated against ND via drinking water. Concurrently, the BRP and sBRP-L/M/H groups received their respective polysaccharides via oral gavage. Parameters assessed included immune organ indices, lymphocyte proliferation, serum antibody titers (HI), cytokine levels (IL-2/IL-6/IFN-γ), and densities of intestinal intraepithelial lymphocytes (IELs) and goblet cells (GCs). Results: sBRP exhibited a selenium content of 30.6 mg/g, with Se-O-C covalent modification confirmed. The sBRP-H group significantly enhanced immune organ indices, lymphocyte proliferation, Newcastle disease virus HI antibody titers, and serum IL-2/IL-6/IFN-γ levels. The sBRP-M group increased IEL and GC densities in the intestine. Conclusions: sBRP acts synergistically with the vaccine to enhance vaccine-induced cellular, humoral, and mucosal immunity, demonstrating promise as a novel oral vaccine immunoenhancer. Full article
(This article belongs to the Section Animal Nutrition)
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