Search Results (131)

Biodegradable Pickering emulsions are attracting increased appeal owing to their promising and diversifying therapeutic applications. In this study, for the first time, a novel therapeutic Pickering emulsion stabilized with ginger powder (GA4) was formulated, characterized, and tested for doxorubicin (DOX) delivery. GA4_Pes physicochemical characterization by DLS (Dynamic Light Scattering), POM (Polarized Optical Microscopy), Cryo-SEM (Cryo-Scanning Electron Microscopy), TEM (Transmission Electron Microscopy), and rheology testing confirmed stability for at least one month, solid-like gel properties, and multiple morphology even at a low concentration of stabilizer. In addition, the morphological, dimensional, and rheological properties of some GA4_Pe loaded with DOX (GA4_Pe@DOX) were examined. These formulations were of the w/o/w type, stable for at least 28 days, and showed efficient doxorubicin internalization. A 24 h in vitro release assay displayed a sustained and pH-dependent release, with 30% and 50% chemotherapeutic released at pH 7.4 and 5.6, respectively. Furthermore, in vitro cell viability assessment performed using GA4_Pe showed no toxicity on immortalized 3T3 mouse embryonic fibroblasts but a small significant inhibitory effect on human breast cancer cell line MCF7. Interestingly, the GA4_Pe@DOX emulsion exerted a cytotoxic effect on MCF7 cells very similar to that of the free DOX solution with the same doses of DOX loaded in the same emulsion. Therefore, the total biocompatibility/biodegradability, good drug entrapment, and high stability, as well as the prolonged release and anti-tumor efficacy maintenance of the loaded drug, suggest a feasible application of ginger powder-based Pickering emulsions for topical delivery as a selective therapeutic platform in targeted formulations of antineoplastic drugs. Full article

The aim of this study was to investigate the prognostic and predictive properties of four specific genes in triple-negative breast cancer (TNBC). We focused on ADIPOQ, GAS5, GATA4, and YAP1, which are known for their roles in key molecular pathways related to tumorigenesis, such as adipokine signaling, lncRNA regulation, transcriptional control, and Hippo signaling, but have not been sufficiently explored in the context of epigenetic regulation in breast cancer. Using the methylospecific PCR (MSP) method, we analyzed the methylation of the four genes in the tumor tissues collected from 57 TNBC patients. We evaluated their association with response to neoadjuvant treatment and clinicopathological characteristics. Additionally, we performed a bioinformatic analysis of methylation and expression data from The Cancer Genome Atlas (TCGA) TNBC cohort to explore their relationships with overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), progression-free interval (PFI), and relapse-free survival (RFS). No significant associations were observed between methylation patterns and clinicopathological characteristics in the patients. However, in silico analysis of the TNBC cohort identified ADIPOQ methylation as having the most significant associations, correlating with all five survival endpoints, including OS, DSS, DFI, PFI, and RFS. GAS5 methylation was significantly associated with OS, DSS, and RFS, and GATA4 methylation showed significant associations with PFI, whereas YAP1 methylation was significantly associated with OS and RFS. In addition, GAS5 expression was linked to DSS, DFI and RFS. This study highlights the potential prognostic significance of the epigenetic regulation of ADIPOQ in TNBC. The in silico findings shed light on the molecular pathways associated with TNBC progression and warrant further investigation to validate their role in clinical outcomes and underlying biological mechanisms. Full article

Background/Objectives: The oral administration of chemopreventive agents for colorectal cancer (CRC) remains limited by their low solubility, instability, and limited intestinal absorption. This study develops sodium carboxymethyl cellulose (CMC)-stabilised water-in-oil-in-water (W/O/W) multiple emulsions as pH-responsive carriers for co-delivery of resveratrol and selenium—two complementary chemopreventive compounds. Methods: Multiple emulsions differing in droplet size (small-droplet emulsions, SDE; large-droplet emulsions, LDE) and CMC concentration (0.0–0.5% w/w) are prepared in a Couette–Taylor Flow contactor. The study involves physicochemical characterisation of emulsions (droplet size, stability, rheological behaviour, ζ-potential, encapsulation efficiency), evaluation of release profiles under simulated gastric pH (2.0) and intestinal pH (7.0) conditions, including pathological environments (pH = 5.5), and ex vivo assessment of mucoadhesion using porcine intestinal tissue. Results: SDE and LDE containing CMC (0.0–0.5% w/w) exhibit a complex “drop-in-drop” structure, with Sauter mean diameters of approximately 9–12 μm and 23–25 μm, respectively, and high encapsulation efficiencies (>91%). Increasing CMC concentration enhances viscosity and induces more negative ζ-potential, confirming polymer adsorption at the oil–water interface. Under simulated gastric pH = 2.0, compound release remains limited (≤15%), whereas gradual/sustained release is observed under simulated intestinal pH (5.5/7.0). Mucoadhesion increases with polymer concentration, reaching ~90% for SDE and ~70% for LDE at 0.5% w/w CMC, and remains above 50% under simulated pathological conditions. Conclusions: The study demonstrates that CMC incorporation improves the structural stability, modulates the release behaviour, and enhances the mucoadhesive properties of W/O/W multiple emulsions. These findings suggest that CMC-stabilised emulsions may be further explored as oral delivery vehicles for CRC chemoprevention. Full article

The utilization of encapsulated biopharmaceuticals, including peptides and proteins, has grown substantially in recent years. In this study, the influence of aliphatic polyester physicochemical properties, specifically crystallinity and hydrophobicity, on the development of protein-loaded microparticles was investigated. A series of polyesters, namely amorphous PDLLA and semicrystalline PLLA, PCL, and PPDL, were synthesized via chemical and enzymatic ring-opening polymerization. Bovine serum albumin (BSA)-loaded microparticles were fabricated using a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation method. The size of microparticles obtained was determined by scanning electron microscopy and dynamic light scattering methods. The enzymatic degradation of the polymer microparticles was assessed through incubation in a lipase-containing buffer solution. BSA and α-chymotrypsin (ACHT) were used as model proteins for the preparation of encapsulated polymer microspheres and comparison of their characteristics and properties. Protein encapsulation efficacy, release rate, and enzyme activity retained after encapsulation were evaluated and compared for selected aliphatic polyesters. The release profiles were processed with the use of various mathematical models to reveal the possible mechanism(s) of protein release. Full article

We investigated the development of IVF porcine embryos incubated in microwells of Well-of-the-Well (WOW) culture dishes. In Experiment 1, 500 embryos were cultured under five different culture conditions: 10 individual embryos in microwells covered by 50 μL PZM-3 medium (50 μL WOW); 10 embryos together in a well of 50 μL PZM-3 (50 μL Well); 10 embryos in microwells covered by 20 μL PZM-3 (20 μL WOW); 10 embryos in a well of 20 μL PZM-3 (20 μL Well); and 10 embryos in a 20 μL drop of PZM-3 in traditional dishes (control). In Experiment 2, the best-performing treatment group from Experiment 1 (50 μL WOW) was further compared to control using a total of 350 embryos. There was no difference in the percentage of cleaved embryos among the groups in both experiments. In Experiment 1, the percentage of blastocysts from 50 μL WOW (42.00 ± 6.29%) was higher (p = 0.001) than in 50 μL Well (29.00 ± 4.58%), 20 μL WOW (13.00 ± 2.13%), 20 μL Well (20.00 ± 2.98%) and control (25.00 ± 5.22%). Similarly, in Experiment 2, blastocyst formation and nuclei number in the blastocysts from 50 μL WOW (37.86 ± 3.95% and 38.97 ± 1.80) were higher (p = 0.040 and p = 0.017) than in the control (28.10 ± 2.64% and 33.21 ± 1.56). The results indicate that individual culture in microwells improves the development of IVF pig embryos. Full article

The production of water-in-water emulsion droplets, the coalescence of which is prevented by adding oil-in-water micrometric droplets, is reported. Hexadecane (O) and cetyl trimethyl ammonium bromide (CTAB) were added to a W/W emulsion made of dextran (Dex)-enriched droplets in a Polyethyleglycol (PEG)-enriched continuous phase, and the mixture was further sonicated. Using Nile red to label the oil droplets enabled the observation of their presence at the surface of Dex droplets (5 µm), allowing for stabilizing them, preventing coalescence of the W/W emulsion, and mimicking W/O/W double emulsions. The addition of sulfate derivative of Dextran (DexSulf) allowed for stable droplets of a slightly larger diameter. By contrast, the addition of carboxymethyl Dextran (CMDex) destabilized the initial aqueous double-like emulsion, yielding sequestration of the oil droplets within the Dex-rich phase. Interestingly, addition of DexSulf to that unstable emulsion re-yielded stable droplets. Similar findings (destabilization) were obtained when adding sodium dodecyl sulfate (SDS) to the initial double-like emulsion, which reformed stable droplets when adding positively charged Dextran (DEAEDex) derivatives. The use of fluorescently (FITC) labeled derivatives of Dextran (Dex, CMDex, DEAEDex, and DexSulf) allowed us to follow their position within, out of, or at the interface of droplets in the above-mentioned mixtures. These findings are expected to be of interest in the field of materials chemistry. Full article

Virtual interactivity in marketing has evolved significantly in recent decades, becoming an essential tool for effectively connecting with consumers in digital environments. Through interactive digital platforms, brands can generate a two-way dialogue with their customers, allowing them to obtain instant feedback and adapt their strategies quickly and effectively. This not only improves but also contributes to strengthening brand love and fostering long-term loyalty. In this context, this research aimed to analyze the effect of virtual interactivity on customer loyalty and WOM through multiple sequential mediation paths, considering the elements of relationship marketing and examining the cognitive (trust–commitment), communicational (communication–conflict management), and experiential (brand love–WOM) mechanisms that operate in digital consumer–brand interactions. A cross-sectional and explanatory study was conducted, considering 417 frequent customers of brands who also follow brands on social media. Participants included women (60.7%) and men (39.3%), ranging in age from 19 to 52 years (M = 30.9 and SD = 6.0). Data were collected using a self-report form on virtual interactivity, relationship marketing, WOW, customer loyalty, and brand love, yielding an appropriate measurement model (α = between 0.791 and 0.908; CR = between 0.791 and 0.916; AVE = between 0.679 and 0.845) which was statistically analyzed using PLS-SEM. The hypotheses confirmed the proposed model, observing the effect of virtual interactivity on important brand factors. This research provides valid results linked to the digital world in banking contexts. Full article

The aim of this study was to develop double emulsions-filled chitosan hydrogel beads for topical application and to elucidate their skin penetration behavior. Double emulsions were prepared by a two-step emulsification method, and double emulsions-filled chitosan hydrogel beads were prepared by the extrusion method. The structure, stability, and skin penetration behavior were investigated. The results of yield efficiency (above 80%) and microstructure observation confirmed the feasibility of the preparation method. After loading the hydrophilic active ingredients (vitamin C) into this system, the retention ratio after storage for 6 weeks increased by 77.6%. Furthermore, hydrogel beads could promote the permeation of hydrophilic active ingredients loaded in double emulsions. When the concentration of chitosan was 3% (w/v), the permeation coefficient of vitamin C from hydrogel beads exhibited an increase (1.7-fold) compared with double emulsions. This system could affect the orderliness of lipid structures in the stratum corneum. In addition, the results indicated that this system could be used for the topical delivery of hydrophobic active ingredients (quercetin) as well. This is the first report of chitosan bead stabilization of W/O/W emulsions, yielding a 2.6-fold increase in skin uptake of hydrophilic actives. Full article

This study aimed to design dual-responsive chitosan–polylactic acid nanosystems (PLA@CS NPs) for controlled and targeted ledipasvir (LED) delivery to HepG2 liver cancer cells, thereby reducing the systemic toxicity and improving the therapeutic selectivity. Two formulations were developed utilizing ionotropic gelation and w/o/w emulsion techniques: LED@CS NPs with a size of 143 nm, a zeta potential of +43.5 mV, and a loading capacity of 44.1%, and LED-PLA@CS NPs measuring 394 nm, with a zeta potential of +33.3 mV and a loading capacity of 89.3%, with the latter demonstrating significant drug payload capacity. Since most drugs work through interaction with DNA, the in vitro affinity of DNA to LED and its encapsulated forms was assessed using stopped-flow and other approaches. They bind through multi-modal electrostatic and intercalative modes via two reversible processes: a fast complexation followed by a slow isomerization. The overall binding activation parameters for LED (cordination affinity, K_a = 128.4 M⁻¹, K_d = 7.8 × 10⁻³ M, ΔG = −12.02 kJ mol⁻¹), LED@CS NPs (K_a = 2131 M⁻¹, K_d = 0.47 × 10⁻³ M, ΔG = −18.98 kJ mol⁻¹) and LED-PLA@CS NPs (K_a = 22026 M⁻¹, K_d = 0.045 × 10⁻³ M, ΔG = −24.79 kJ mol⁻¹) were obtained with a reactivity ratio of 1/16/170 (LED/LED@CS NPs/LED-PLA@CS NPs). This indicates that encapsulation enhanced the interaction between the DNA and the LED-loaded nanoparticle systems, without changing the mechanism, and formed thermodynamically stable complexes. The drug release kinetics were assessed under tumor-mimetic conditions (pH 5.5, 10 mM GSH) and physiological settings (pH 7.4, 2 μM GSH). The LED@CS NPs and LED-PLA@CS NPs exhibited drug release rates of 88.0% and 73%, respectively, under dual stimuli over 50 h, exceeding the release rates observed under physiological conditions, which were 58% and 54%, thereby indicating that the LED@CS NPs and LED-PLA@CS NPs systems specifically target malignant tissue. Release regulated by Fickian diffusion facilitates tumor-specific payload delivery. Although encapsulation did not enhance the immediate cytotoxicity compared to free LED, as demonstrated by an in vitro cytotoxicity in HepG2 cancer cell lines, it significantly enhanced the therapeutic index (2.1-fold for LED-PLA@CS NPs) by protecting non-cancerous cells. Additionally, the nanoparticles demonstrated broad-spectrum antibacterial effects, suggesting efficacy in the prevention of chemotherapy-related infections. The dual-responsive LED-PLA@CS NPs allowed controlled tumor-targeted LED delivery with better selectivity and lower off-target toxicity, making LED-PLA@CS NPs interesting candidates for repurposing HCV treatments into safer cancer nanomedicines. Furthermore, this thorough analysis offers useful reference information for comprehending the interaction between drugs and DNA. Full article

Introduction: The evaluation of lymph nodes (LNs) in patients with suspected oncological disease is a crucial factor influencing further diagnostics and management. However, there is a lack of a dedicated system for the precise and comprehensive assessment of LNs. To address this gap, we developed the Lymph Node Reporting and Data System (LN-RADS). Methods: This retrospective multiparametric analysis included the assessment of 719 LNs in 489 patients. The images were evaluated by three radiologists using the LN-RADS scale, assigning each case to one of six group: 1 (normal), 2 (steatotic), 3 (reactive), 4a (low suspicion of malignancy) vs. 4b (high suspicion of malignancy), and 5 (definitely malignant) and were then correlated with histopathological results. The diagnostic performance of LN-RADS was validated. The analysis of 12 morphological features of LNs was performed to identify predictors of malignancy. Results: Histopathological analysis confirmed 389 malignant and 330 benign LNs. LN-RADS achieved 89% sensitivity, 85% specificity, and 87% accuracy in the diagnosis of malignant LN. The observed risk of malignancy by group was 0% for LN-RADS 1, 0% for LN-RADS 2, 2% for LN-RADS 3, 31% for LN-RADS 4a, 77% for LN-RADS 4b, and 97% for LN-RADS 5. Cohen’s kappa statistic indicated substantial inter-reader agreement. Among the evaluated features, the strongest predictor of malignancy was the cortex thickness diameter, with a threshold value of ≥6 mm (82% accuracy; AUC = 0.894). Conclusions: This study demonstrated the high efficacy of the LN-RADS system in distinguishing between benign and malignant lymph nodes and in stratifying malignancy risk. It also showed substantial inter-rater agreement. Full article

Biomimetic peptides represent a growing class of active ingredients in modern cosmeceuticals, designed to mimic the function of the naturally occurring peptides involved in skin homeostasis, repair, and regeneration. Among them, acetyl hexapeptide-8 (AH-8), often referred to as a “botox-like” peptide, has received considerable attention for its potential to dynamically reduce wrinkles through the modulation of neuromuscular activity. AH-8 is widely used in topical formulations intended for anti-aging effects, scar treatment, and skin rejuvenation. This review provides a comprehensive overview of the structure and proposed mechanisms of action of AH-8, with particular focus on its efficacy and skin penetration properties. Due to its hydrophilic nature and relatively large molecular size, AH-8 faces limited permeability through the lipophilic stratum corneum, making effective dermal delivery challenging. Formulation strategies such as oil-in-water (O/W) and multiple water-in-oil-in-water (W/O/W) emulsions have been explored to enhance its delivery, but the ability of AH-8 to reach neuromuscular junctions remains uncertain. Preclinical and clinical studies indicate that AH-8 may reduce wrinkle depth, improve skin elasticity, and enhance hydration. However, the precise biological mechanisms underlying these effects—particularly the peptide’s ability to inhibit muscle contraction when applied topically—remain incompletely understood. In some studies, AH-8 has also shown beneficial effects in scar remodeling and sebum regulation. Despite promising cosmetic outcomes, AH-8’s low skin penetration limits its bioavailability and therapeutic potential. This review emphasizes the need for further research on formulation science and delivery systems, which are essential for optimizing the effectiveness of peptide-based cosmeceuticals and validating their use as non-invasive alternatives to injectable treatments. Full article

Tannic acid (TA) possesses antioxidant, anticancer, and antibacterial properties. However, its pH sensitivity, protein cross-linking properties, and susceptibility to oxidation restrict its application. To address these challenges, W/O/W multiple emulsified TA microcapsules were developed using soybean protein isolate (SPI) as the natural wall material emulsifier through a two-step emulsification and spray drying process. The encapsulation efficiency of the obtained TA microcapsules was 87.6%, and TA’s thermal stability was significantly improved. TA microcapsules effectively reduced the acidity and irritability of TA, eliminated protein flocculation, and enhanced biocompatibility. Notably, the cell viability of the TA microcapsule (>94%) was significantly higher than free TA (65.6%). The storage stability test revealed that the microcapsules maintained structural integrity, with a retention rate of 96% after 10 days of storage. In vitro release studies of TA microcapsules demonstrated a sustained-release effect within 24 h. Simulated digestion studies further elucidated the protective effect of microcapsules on TA during gastric digestion. These multi-structured microcapsules based on SPI effectively address the limitations associated with TA utilization and enhance its potential for dual oral/transdermal administration in biomedical and cosmetic applications. Full article

Natural pigments like betacyanins are highly unstable under heat, light, acid, and alkaline conditions. Yeast protein (YP) is a promising substitute protein, while chitooligosaccharides (COS) are water-soluble alkaline polysaccharides. Water-in-oil-in-water (W₁/O/W₂) emulsions, with two-membrane, three-phase structure, can serve as effective carriers for stabilizing pigments. In this study, YP-COS complexes formed through electrostatic interactions were used as hydrophilic emulsifiers to create betacyanin-coated W₁/O/W₂ emulsions. The W₁/O colostrum was designed to make up 30%, 70%, and 90% of the emulsion (v/v)and the W₂ was designed by the complexes with three concentrations of YP (2%, 1.25% and 0.5%, w/v)-COS (6%, 3.75% and 1.5%, w/v). The optimal formulation was determined through comprehensive evaluation of micromorphological characteristics, particle size, zeta potential and creaming index, ultimately yielding a system comprising YP (2%)-COS (6%) and 90% W₁/O colostrum. Moreover, the W₁/O/W₂ emulsion system significantly improved the betacyanins retention under thermal treatment, photolytic exposure, pH gradients, and extended storage compared to the betacyanin aqueous solution (p < 0.05). In vitro digestion tests showed the emulsion retained 58.39% of betacyanins, while the betacyanin aqueous solution retained only 41.42%, demonstrating the emulsion’s ability to delay the betacyanins release, offering new insights for using YP-COS complexes in food production and other fields. Full article

Background: Influenza virus is one of the major respiratory virus infections that is a global health concern. Although there are already approved vaccines, most are administered via the intramuscular route, which is usually painful, leading to vaccine hesitancy. To this end, exploring the non-invasive, transdermal vaccination route using dissolving microneedles would significantly improve vaccine compliance. Research on innovative vaccine delivery systems, such as antigen-loaded PLGA microparticles, has the potential to pave the way for a broader range of vaccine candidates. Methods: In this proof-of-concept study, a combination of the inactivated influenza A H1N1 virus and inactivated influenza A H3N2 virus were encapsulated in a biodegradable poly (lactic-co-glycolic acid) (PLGA) polymeric matrix within microparticles, which enhanced antigen presentation. The antigen PLGA microparticles were prepared separately using a double emulsion (w/o/w), lyophilized, and characterized. Next, the vaccine microparticles were assessed in vitro in dendritic cells (DC 2.4) for immunogenicity. To explore pain-free transdermal vaccination, the vaccine microparticles were loaded into dissolving microneedles and administered in mice (n = 5). Results: Our vaccination study demonstrated that the microneedle-based vaccine elicited strong humoral responses as demonstrated by high antigen-specific IgA, IgG, IgG1, and IgG2a antibodies in serum samples and IgA in lung supernatant. Further, the vaccine also elicited a strong cellular response as evidenced by high levels of CD4+ and CD8a+ T cells in lymphoid organs such as the lymph nodes and spleen. Conclusion: The delivery of influenza vaccine-loaded PLGA microparticles using microneedles would be beneficial to individuals experiencing needle-phobia, as well as the geriatric and pediatric population. Full article

Augmented Reality (AR) enables users to see or interact with virtual objects in real-world environments. This case study examines three AR lessons integrated into a beginner-level Spanish course at a university. The participants were 18 undergraduate students enrolled in this class. The AR lessons portrayed a classroom, a coffee shop, and a family setting aimed at improving students’ retention of Spanish vocabulary related to each AR environment. The research data included pre-test and post-test scores, in-class observations, and interviews. Paired-sample t-tests were conducted before and after the AR sessions to examine vocabulary retention. The quantitative findings revealed significant differences in test scores among all three interventions, suggesting the efficacy of AR-based learning methods. A thematic analysis was conducted on qualitative data, encompassing interviews with six students and in-class observations. Students shared that the AR-based lessons made learning more engaging and enhanced vocabulary recall. Student interactions increased, and the AR-based lessons inspired students to transition from technology users to designers. This study addresses the need for more AR learner-centered empirical studies in learning Spanish and provides implications for AR educational application design and implementations. Full article