Search Results (2,254)

The growing demand for effective delivery of active ingredients in cosmetic formulations has stimulated the development of advanced carrier systems. This study evaluates the potential of the dicephalic di-N-oxide surfactant N,N-bis [3,3-(dimethylamino)-propyl]dodecylamide (C₁₂-(DAPANO)₂) as a stabilizer for aqueous dispersions of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). Lipid nanoparticles were prepared using three classes of solid lipids—cetyl palmitate, glyceryl behenate, and stearic acid—through high-speed homogenization followed by ultrasonication. Their physicochemical properties were characterized using DLS, TEM, AFM, DSC, and TGA. All formulations exhibited particle sizes below 300 nm and a low polydispersity index (<0.30), indicating good uniformity. High absolute zeta potential values and stability studies confirmed excellent physical stability, with all dispersions remaining stable for at least 90 days at room temperature. Compared with bulk lipids, nanoparticles showed lower melting temperatures and reduced crystallinity. NLCs exhibited lower crystallization and melting temperatures than SLNs and displayed a more spherical morphology. Cytotoxicity assessment using J774.E macrophages revealed no adverse effects. These findings highlight the surfactant’s potential as a stabilizing agent for lipid-based cosmetic nanocarriers, supporting the development of stable systems with improved active ingredient loading and controlled release properties. Full article

Background/Objectives: The aim of current study was the significant improvement of both the flowability and the compressibility of mesoporous silica microparticles (MSMs), to enable the formulation a potential drug delivery system. MSMs are of emerging interest in the pharmaceutical industry, due to their numerous advantages and versatile applicability, such as improvement in aqueous solubility and epithelial permeability, thus enhancing the oral bioavailability of drugs. However, the formulation of these types of materials has been a major challenge. This problem originates from poor powder flow characteristics due to particle properties. Methods: A binder-free high-shear wet granulation (HSWG) process was performed to improve the flowability and compressibility of the model material, meanwhile preserving its porosity. The prepared granules were characterized by particle size, size distribution, yield percentage, particle morphology, porosity, powder flowability, crushing strength, and stability. Micro-CT measurements were performed to examine the structure of the granules and to see the internal segmentation resulted by the two-step granulation process. The granules were compressed into tablets to evaluate the compressibility behavior based on the models of Kawakita and Walker. The physical parameters of the compressed tablets, such as breaking hardness, tensile strength, and thickness, were tested. Results: The prepared granules were evaluated successfully according to the mentioned properties and found to be satisfactory compared to the raw materials. The binder-free method appeared to be effective, thus the use of binders may be avoided if the process is designed well and critical process parameters (CPPs) selected carefully. The granules showed good stability over a one-year testing period. The micro-CT test also verified the success of the initial concept of preparing core–shell structured granules, and enabled the determination of macropores. Nevertheless, the results were completed with BET measurements to determine specific surface area of the granules. Conclusions: The effect of the critical process parameters of the granulation process on all the mentioned attributes was investigated and since major differences were observed between the batches, the effect of the selected CPPs were also verified. Full article

Background: Effective strategies for delivering neuroprotective agents to the brain remain a major challenge due to the poor solubility, rapid metabolism, and low bioavailability of promising molecules, such as 7,8-dihydroxyflavone (7,8-DHF). This small-molecule TrkB receptor agonist exhibits significant antioxidant, neuroprotective properties, and additional effects on metabolic regulation, but its therapeutic potential is limited by unfavorable pharmacokinetic characteristics. Nanotechnology-based delivery systems are increasingly explored to improve drug stability, enhance bioavailability, and facilitate direct nose-to-brain transport following intranasal administration. In this study, lipid nanoparticles encapsulating 7,8-DHF were developed using a fish-oil-based lipid core enriched with ω-3 polyunsaturated fatty acids (DHA and EPA) and naturally derived excipients, including soybean lecithin and ε-polylysine. Methods: The formulation was optimized using a Design of Experiments (DoE) approach based on a 2³ full factorial design, evaluating drug concentration, lecithin concentration, and surfactant type (Pluronic^® F127 or Tween^® 80). The main formulation responses considered were particle size, polydispersity index (PDI), zeta potential, and encapsulation efficiency. Results: The optimized nanoparticles exhibited nanometric dimensions (<250 nm); spherical morphology, confirmed by TEM; low polydispersity (PDI < 0.3); and adequate encapsulation efficiency. Stability studies in simulated biological fluids indicated good physicochemical stability for up to 48 h, while interaction studies with mucin suggested a good interaction within the mucus environment. ROS scavenging capacity was confirmed through the DPPH chemical assay, and in vitro experiments on olfactory ensheathing cells, selected as a biologically relevant model for their anatomical localization along the olfactory pathway, showed reduced cytotoxicity of the encapsulated drug compared with the free form. Conclusions: Collectively, these results support the potential application of the developed nanoformulation in the intranasal delivery of 7,8-DHF. Full article

The Five Domains Model has become one of the most widely adopted frameworks in animal welfare science and practice. The Model is now applied in a range of ways; among the most prominent are (1) as a framework for systematic and structured welfare assessment and (2) as an organising structure for planning and communicating appropriate (i.e., welfare-focused) care provisions, education, and standards. This paper focuses on these two applications and proposes a corresponding update to the affiliated Five Provisions and Welfare Aims. Specifically, we revise: (1) Provision 4 from “Appropriate Behaviour” to “Appropriate Choices” to reflect the 2020 update of the Model incorporating human–animal interactions and the 2023 operationalisation of agency in Domain 4; (2) Provision 2 from “Good Environment” to “Good Living Space” to resolve ambiguity with Domain 4’s “Interactions with the Environment”; and (3) Provision 5 from “Positive Mental Experiences” to “Integrated Care,” which captures consistent delivery of the first four provisions over time and across all those who interact with the animal. This update also pairs Provision 5 with a welfare aim that specifies the integrated mental state the animal should experience as a result. This change makes the distinction between care (provisions) and welfare (aims) consistent throughout the framework. It also makes explicit the integrative role of Provision 5, which parallels Domain 5’s role in the Model. We then describe the reasoning process that distinguishes welfare assessment from welfare-focused care provision. Welfare assessment uses the domain structure as a reasoning pathway, with the assessor using indicators and their impacts in Domains 1 to 4 to infer named mental (affective) experiences in Domain 5. Planning and communicating appropriate (i.e., welfare-focused) care uses the same structure to organise information about what is provided to animals, without executing the inferential step to Domain 5. Drawing on examples from organisations that use the Model for different purposes, we show that both applications are legitimate but produce different outputs. The Five Provisions framework, with its dual structure of provisions paired with welfare aims, serves the care planning and communication function more effectively than does the Model’s domain structure alone. Recognising these different uses also helps to locate where recent critiques of the Model apply and where they do not. Finally, we propose that the provisions and welfare aims framework can supplement “needs” language in legislation and policy to better reflect the distinction between animal care and animal welfare. Full article

The combination of chemotherapy and immunotherapy represents a promising approach that leverages their complementary benefits. However, the side effects resulting from off-target effects and the low efficiency of immune activation remain a significant concern. Herein, we developed a zinc-doped calcium phosphate (ZCP) nanocarrier for the delivery of the chemotherapeutic drug doxorubicin (DOX). By further encapsulating whole proteins from 4T1 breast cancer cells, we constructed a novel nanodrug delivery system named ZCPDM. This system enables specific targeting of tumor cells and undergoes intracellular degradation to release DOX, Zn²⁺, and Ca²⁺. As a chemotherapeutic agent, DOX induces apoptosis while significantly elevating intracellular reactive oxygen species (ROS), thereby enhancing cytotoxicity. This leads to DNA damage and the release of chromosomal fragments. These DNA fragments, together with Zn²⁺, activate the cGAS-STING signaling pathway and trigger pyroptosis, which promotes more efficient recognition and clearance of tumor cells by the immune system. Through these dual mechanisms, ZCPDM effectively combines chemotherapy and immunotherapy. The anti-tumor efficacy and underlying mechanisms were validated at the cellular level. Furthermore, studies in tumor-bearing mice demonstrated its robust anti-tumor performance and ability to suppress tumor recurrence, along with good biosafety. This targeted drug delivery system achieves safe and synergistic chemo-immunotherapy through homologous targeting-mediated pyroptosis and activation of the cGAS-STING pathway, offering a novel and promising strategy for cancer treatment. Full article

Objectives: An integrated methodological framework was developed for modeling and multiobjective optimization of sustained-release drug delivery systems. Methods: The cumulative release percentage was fitted as a function curve, and functional principal component analysis was subsequently used to transform the function curves into functional principal component scores (FPCs). FPCs were then treated as dependent variables, while the proportions of the formulation factors were used as independent variables to construct Scheffé polynomial regression models. Finally, Non-dominated Sorting Genetic Algorithm III (NSGA-III) was applied to perform multi-objective optimization. Results: FPC1, FPC2, and FPC3 captured 95.18%, 4.39%, and 0.32% of the total variation, respectively. Corresponding Scheffé polynomial regression models were established, including quadratic models for FPC1 (adjusted R² = 0.751, AIC = 168.557) and FPC2 (adjusted R² = 0.592, AIC = 119.302), and a special cubic model for FPC3 (adjusted R² = 0.597, AIC = 64.574). The NSGA-III algorithm generated a Pareto optimal set, yielding stable formulation compositions with mean (SD) values of X₁ = 0.123 (0.015), X₂ = 0.821 (0.032), X₃ = 0.012 (0.017), and X₄ = 0.045 (0.015). The corresponding FPCs were −41.787 (2.544), 10.009 (0.168), and 8.264 (0.010) for FPCs1–FPCs3, respectively. The reconstructed cumulative release percentages were 42.471 (1.661), 52.623 (2.868), 69.942 (1.200), 84.275 (1.010), and 93.330 (0.832), demonstrating good agreement with the target release profiles. Conclusions: The integrated FDA–Scheffé–NSGA-III framework provides a robust and effective approach for accurately modeling release behavior and optimizing sustained-release formulations. Full article

Background: Clear post-extraction sessions are vital for good patient outcomes. Traditional methods, such as verbal and printed information, have historically been prevalent; however, digital health care methods for analysis and communication are increasingly being adopted. Still, evidence comparing preferences for digital versus traditional instruction, especially for routine post-extraction care, remains limited. Objectives: This study aimed to evaluate preferences between digital methods (QR code-based videos) and traditional methods (verbal and printed leaflets) for delivering post-extraction care instructions among dental patients and students. It also assesses perceptions of communication quality, confidence, and patient interaction associated with each method. Methods: A cross-sectional study involved 200 dental students and 200 patients undergoing routine tooth extractions. The sample size was determined based on a 5% margin of error at a 95% confidence level for proportion estimation. Participants experienced all three instructional delivery methods—verbal, printed leaflet, and QR code-based video—for post-extraction care and completed validated questionnaires. The study assessed preferences for each delivery method, communication quality, confidence in following or providing instructions, ease of access, perceived usefulness, and impact on patient-provider interaction. Data were analyzed using descriptive statistics, the Mann–Whitney U test for group comparisons, and Spearman correlation for relationships among ordinal data. Results: Among all participants, 67.5% chose QR codes as the preferred method for improving communication (p < 0.001). Among dental students, 49% favored QR codes as the best method for postoperative instructions, and 50.5% indicated that QR codes boosted their confidence in providing instructions to patients. Preference for QR codes ranged from 43.5% to 65.5% across different aspects evaluated. Notably, among patients aged 60 years or older, 65.5% considered QR codes the most convenient for the elderly. Mann–Whitney U tests showed statistically significant differences between students and patients for ease of access (p = 0.009, rank biserial r = −0.143), video length appropriateness (p = 0.003, rank biserial r = −0.160), and the unlikelihood of missing instructions (p < 0.001, rank biserial r = −0.446). Conclusions: QR code-based video instructions were widely preferred over traditional methods by both dental students and patients for post-extraction care delivery. These findings support the integration of digital communication tools into post-extraction care protocols as a complement to traditional instruction delivery methods, though longitudinal studies assessing actual clinical outcomes are needed. Full article

Cancer is still one of the world’s major causes of morbidity and mortality; thus, safer and more efficient treatment approaches are required. The structural variety, multitargeted mechanisms, and generally good safety profiles of plant-derived polyphenols have made them attractive anticancer medicines. Flavonoids (like quercetin), stilbenes (like resveratrol), phenolic acids and curcuminoids (like curcumin) are major classes that have shown strong anticancer action against a variety of cancers, including prostate, colorectal and breast cancers. Through targets including PI3K/Akt, MAPK, NF-κB, and p53 signaling networks, these substances influence important molecular pathways involved in tumor initiation and development, including oxidative stress, inflammation, apoptosis, cell cycle control, angiogenesis and metastasis. The clinical translation of polyphenols is still constrained by poor bioavailability, fast metabolism, low aqueous solubility and inefficient pharmacokinetic characteristics, which lead to insufficient systemic exposure and therapeutic efficacy despite strong preclinical data. Their therapeutic applicability is further complicated by variations in absorption and possible dose-related restrictions. To overcome these limitations, the anticancer efficacy of polyphenols has been enhanced via delivery technologies like polymeric nanoparticles, lipid-based carriers, nanoemulsions and phytosome complexes, which have shown improved stability, increased bioavailability and targeted delivery to tumor tissues. This review provides a comprehensive and integrative analysis of plant-derived polyphenols by linking molecular mechanisms, pharmacokinetic limitations and emerging delivery strategies within a translational framework. By bridging these interconnected domains, this review highlights the potential of polyphenols as viable candidates in next-generation cancer therapeutics and underscores the need for well-designed clinical studies to facilitate their successful integration into oncology practice. Full article

This study examined Kefiran, an exopolysaccharide derived from milk kefir grains, as a novel biopolymer for encapsulating phenolic extracts from sunflower cake and its antimicrobial properties in the development of natural and functional food ingredients. Kefiran was obtained from kefir grains using three extraction protocols: hot water (M1), hot water with 30% trichloroacetic acid (M2), and mild heat combined with ultrasound at 60 °C (M3). The ultrasound-assisted method produced the highest carbohydrate concentration. Spectrophotometric assays (phenol–sulfuric and Bradford), Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, and water-holding capacity were employed to characterize the composition, structure, and morphology of the extracts, revealing well-preserved polysaccharide fingerprints and a highly porous microstructure, consistent with their potential application in food systems. Kefiran was then evaluated as an encapsulating agent in complex coacervation at pH 3.75, using three Kefiran-based wall formulations (M1, M2, and M3) with gum arabic and whey protein isolate (WPI) as co-wall materials, and their performance was compared with gum arabic and WPI controls. Across formulations, coacervate microcapsules achieved high encapsulation efficiencies (83–93%), tunable particle sizes, and predominantly negative zeta potentials, indicative of good colloidal stability. The Kefiran extract and coacervate microcapsules demonstrated significant antioxidant and antimicrobial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans, with minimum inhibitory concentrations ranging from 250 to 1000 µg/mL. The findings support ultrasound-extracted Kefiran as a multifunctional biopolymer suitable for bioactive delivery and as a natural antimicrobial component in advanced functional food formulations. Full article

Background: Pregnancies tend to progress without any serious complications. Nonetheless, for a subset of women, obstetric complications may develop, ranging in severity. The most critical of these life-threatening events is referred to as Maternal Near Miss (MNM). To identify the epidemiological and obstetric characteristics, as well as clinical outcomes of MNM cases reported over the year 2021 in the Brazilian state of Paraná. This quantitative, population-based study analyzed 888 notifications that occurred in 2021, obtained from the MNM Notification System. Descriptive statistics and a one-sample Chi-square goodness-of-fit test were applied to the data. Among the women reported, 92.6% were pregnant, the mean age was 29 years, 67.1% identified as white, and 45.2% had preexisting health conditions. Regarding obstetric characteristics, 41.6% were classified as high-risk pregnancies, but nearly one-third (32.3%) of MNM cases occurred in women initially classified as usual risk. The clinical worsening event occurred most frequently during the third trimester (71.9%), and emergency cesarean section was indicated in 60.1% of cases with complete information for this variable. Cesarean delivery predominated over vaginal delivery, with an emergency-to-elective cesarean ratio of approximately 4.7:1. Most women (75%) were discharged after recovery. MNM events are not restricted to women initially classified as high-risk, underscoring the need to strengthen early detection strategies and ensure appropriate management at all levels of care. Improved training of healthcare professionals responsible for reporting and the standardization of MNM monitoring systems in Brazil are also essential. Full article

With the development of the low-altitude economy, low-altitude intelligent agents such as delivery robots, courier drones, and outdoor cleaning robots are gradually moving towards widespread application. One of the core challenges faced by such systems is localization and mapping in complex scenarios characterized by satellite signal denial and unknown environmental prior information. To address this requirement, this paper proposes ESKF-g2o-SLAM, a stereo visual-inertial SLAM system that integrates an ESKF (Error-State Kalman Filter)-based visual-inertial odometry front-end with an ORB-feature-based g2o graph optimization back-end in a cascaded, loosely coupled manner. The proposed method was evaluated on 11 sequences of the EuRoC dataset and compared with state-of-the-art approaches including ORB-SLAM2 (stereo), MSCKF-VIO, OKVIS, and VINS-Fusion (stereo). Ablation studies show marginal improvements on selected sequences and suggest potential robustness advantages under more challenging visual conditions. Experimental results show that our method achieves competitive accuracy in terms of both Absolute Trajectory Error (ATE) and Relative Pose Error (RPE), exhibiting good robustness and stability. Full article

Background: Restless legs syndrome (RLS) is very common among pregnant women; its prevalence corresponds to parity and occurs more frequently in the later stages of pregnancy. It is associated with numerous adverse pregnancy outcomes such as an increased risk of Caesarean section, preeclampsia, insomnia, and depression. Medical treatment of RLS during pregnancy is challenging considering the risks to both the mother and fetus. Case Description: In this report, we describe the case of a 44-year-old, seventh-time multiparous woman with a positive family history of RLS who presented with severe symptoms in her 24th week of pregnancy. She has had symptoms of RLS in every pregnancy thus far, usually starting in the second trimester, with an ineffective therapeutic response to diazepam and uncomfortable sensations, which usually resolve spontaneously a few weeks after delivery. After replacing diazepam with low-dose clonazepam, the patient reported complete disappearance of unpleasant sensations in her legs, with a significant improvement in her quality of life. Conclusions: A low dose of clonazepam is a good therapeutic option for the treatment of RLS during pregnancy and, if necessary, can also be considered the therapy of choice during lactation. Full article

Microneedles are a new technology in transdermal drug delivery that allows for the pain-free administration of drugs. Recently, these microneedles have gained popularity compared to traditional injections. Nevertheless, the selection of the most suitable materials is a significant issue, requiring a systematic analysis of various performance parameters. This paper developed a multi-criteria decision-making model based on the analytic hierarchy process (AHP) to systematically evaluate four primary material types for therapeutic microneedle applications: polymers, metals, ceramics, and silicon. The researchers defined five performance criteria, ranked by importance: biocompatibility (48.8%), mechanical properties (25.3%), manufacturability (15.8%), cost-effectiveness (6.6%), and compatibility with different types of microneedles (3.5%). The validity of the framework was established using the TOPSIS and ELECTRE methods, which showed strong agreement in the rankings, and a sensitivity analysis revealed that the rankings did not change with a ±20% variation in the parameters in 95% of the cases. The outcomes indicated that polymers are the most suitable, with the highest global priority score (38.3%), and they are good in biocompatibility (53.0% local priority), manufacturability (53.3%), and relative cost advantages (62.2%), though medical-grade polymer costs remain substantial. Metals were placed second (31.8%) due to their better mechanical properties (50.3%), followed by ceramics (17.6%) and silicon-based materials (12.3%). The framework offers clear decision guidelines: polymers for dissolving microneedle systems and controlled drug release applications; metals for precise liquid delivery devices; ceramics for specialized pharmaceutical uses that require extreme chemical compatibility; and silicon for research applications requiring precise geometries. Full article

Bacterial outer membrane vesicles (OMVs) are spherical structures made up of a double layer, they are each nanostructured (20–300 nm), and they are released from all populations of Gram-negative bacteria. The purpose of this review is to synthesize a comprehensive summary of the current state of knowledge about OMV biogenesis, function in biology, and application to biomedical engineering. Using these three known biogenesis mechanisms as a basis for this review, we discuss the mechanisms of OMV biogenesis that have been described as conserved: (1) disruption of outer membrane–peptidoglycan links. (2) periplasmic stress-driven adaptive release is associated with bilayer lipid asymmetry and the use of signaling molecules. OMVs are considered to be “public goods” for the microbe, allowing for nutrient acquisition, resistance to antibiotics, and the potential for horizontal gene transfer between microbes. OMVs exhibit a different duality at the interface of the pathogen host, where the pathogenic OMV is the delivery vehicle for virulence factors and pathogen-associated molecular patterns (PAMPs) leading to host immune response, while the symbiotic OMV (e.g., those produced by Bacteroides fragilis (Bact. fragilis)) promote regulatory T cell differentiation and mucosal tolerance. The review also addresses the various techniques currently available to isolate OMVs (e.g., ultracentrifugation and size-exclusion chromatographic techniques) and presents engineered/alloying strategies (e.g., genetic modifications to tolR/msbB and surface functionalization) to enhance the viability, safety, and specificity of OMVs for biomedical delivery. Finally, the review addresses significant obstacles related to standardization, batch variation, and in vivo safety associated with synthetic or personalized therapeutics based on OMVs, providing some recommendations for future research in this area. Full article

Background: Interest in advanced wound dressings for clinical applications is increasing, with biopolymer-based formulations emerging as an effective strategy for wound management. Objectives: This study aimed to develop and characterize sponge-like biopolymeric matrices for the topical delivery of indomethacin as a model anti-inflammatory drug. Methods: Matrices were prepared by combining collagen and methylcellulose (MC) gels in varying ratios, followed by lyophilization. Physicochemical characterization included FT-IR, SEM, contact angle, and water absorption analysis. Biological evaluation involved enzymatic degradation, while biopharmaceutical and pharmacological assessments included in vitro drug release and in vivo testing in Wistar rats with experimentally induced burns. Results: FT-IR analysis confirmed that collagen’s triple-helical structure was preserved in the presence of MC and indomethacin for the samples with maximum 25% methylcellulose. SEM analysis revealed a microporous network with integrated cellulose fibers, where pore size decreased with higher MC content. Compressive strength measurements demonstrated enhanced mechanical resistance with increasing MC content, indicating improved structural stability of the matrices. Moreover, increased MC content led to higher contact angle values but maintained hydrophilicity, while formulations with up to 25% MC exhibited good absorption capacity and structural integrity. Enzymatic degradation studies confirmed that matrices with at least 75% collagen content maintained their structural integrity over time, favoring prolonged application and sustained drug delivery. In vitro drug release followed a biphasic profile, supporting rapid initial anti-inflammatory action followed by gradual release of the drug. In vivo animal studies demonstrated accelerated wound healing in treated rats for all tested matrices. Conclusions: Overall, the developed indomethacin-loaded biopolymeric matrices showed promising structural, functional, and therapeutic properties for effective wound treatment. Full article