Search Results (1,366)

Background/Objectives: Psoriasis is a chronic, immune-mediated inflammatory skin disorder affecting millions of individuals worldwide. It remains a therapeutic challenge due to the limited skin penetration of many drugs, adverse systemic effects, and the need for long-term management. Transferosomal nanoformulations containing natural products were proposed as a potential therapeutic tool. Methods: Transferosomes containing 20-hydroxyecdysone and resveratrol were prepared using the thin-film hydration method followed by probe ultrasonication, generating several formulation variants differing in composition. The vesicles were characterized by dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) to determine size, polydispersity index (PDI), and zeta potential. Furthermore, time-domain nuclear magnetic resonance (TD-NMR) relaxation measurements were employed to evaluate local molecular dynamics and membrane fluidity, providing deeper insights into the structural integrity and elasticity of the transferosomal systems. The stability of the nanoformulations was assessed for one month in water and phosphate-buffered saline (PBS). Viability was evaluated in vitro using the MTS assay on human epidermal keratinocyte (HEK) and psoriasis-patient derived human epidermal keratinocyte (PHEK) cell lines, alongside antimicrobial profiling against four representative human skin microbiome strains. Acute toxicity was further examined in vivo using the Danio rerio FET test. Results: The formulations demonstrated high physicochemical stability over the tested period, maintained desirable particle sizes within 100–200 nm, and showed no cytotoxicity toward skin-associated bacteria or in the zebrafish model. Conclusions: The developed nanoformulations present suitable properties in terms of safety and stability and can be considered for potential use in psoriasis treatment. Full article

In this study, a pH-responsive chondroitin sulfate–methotrexate (MTX) polymeric prodrug was synthesized through Schiff base formation between oxidized chondroitin sulfate and MTX. The resulting amphiphilic conjugate exhibited a conjugation degree of 184 mg MTX per g conjugate and spontaneously self-assembled into stable nanoparticles (CSMXPs) with a mean diameter of 120 ± 10 nm, a polydispersity index of 0.24, and a critical aggregation concentration of 4.7 × 10⁻⁴ mg mL⁻¹. Drug release studies demonstrated a marked pH-dependent behavior, with complete MTX release after 24 h at pH 5.0 and a sustained release profile under physiological conditions. The release mechanism followed reversible first-order kinetics and was accelerated by acid-catalyzed hydrolysis of the imine linkage. Biological evaluation revealed enhanced therapeutic selectivity of CSMXPs compared with free MTX. At 36 μM MTX-equivalent concentration, CSMXPs reduced HeLa cell viability to 37%, while maintaining MCF-10A viability above 88%, whereas free MTX decreased viability in both cell lines (51% and 65%, respectively). Fluorescence confocal microscopy confirmed efficient nanoparticle uptake by cancer cells. These findings demonstrate that CSMXPs represent a promising self-assembling nanoprodrug platform for selective and targeted cancer therapy. Full article

Objectives: The present study was designed to repurpose aripiprazole (AR) as an antifungal drug for the management of topical candidiasis using a bioadhesive sponge incorporating a hyaluronic acid (HA)-, ceramide-, and terpene-based vesicular nanosystem (HCT-NS). Methods: AR-loaded HCT-NS were formulated by the modified ethanol injection method with varying amounts of HA, ceramide, and two types of terpenes. The formulation optimization of AR-loaded HCT-NS was carried out by a full factorial design. The responses evaluated were zeta potential (ZP), particle size (PS), and entrapment efficiency (EE). Results: The optimized AR-loaded HCT-NS has 5 mg of HA, 10 mg of ceramide, and fenchone, which showed spherical vesicles with EE of 81.21 ± 0.01%, PS of 223.25 ± 11.25 nm, polydispersity index (PDI) of 0.492 ± 0.003, and ZP of −27.74 ± 0.04 mV. The optimum HCT-NS showed a greater drug release in comparison to the AR suspension. In addition, the selected HCT-NS exhibited good bioadhesive characteristics and stayed stable during storage. Confocal laser scanning microscopy confirmed the penetration of the fluorescently optimized HCT-NS via the skin. Further, the scanning electron microscope image indicates the porous structure of the formed sponge. In vivo evaluations for the optimum HCT-NS sponge showed a good antifungal impact against Candida albicans. The safety of topical treatment was confirmed by histopathological examination. Conclusions: Taken together, the results here suggest that the AR-loaded HCT-NS sponge showed potent antifungal activity against Candida albicans fungal infection. Full article

Lycium barbarum polysaccharides are major bioactive constituents of Lycium barbarum fruit and are widely recognized for antioxidant, immunomodulatory, and intestinal protective activities. Selenium nanoparticles are considered a safer selenium formulation than conventional inorganic selenium because they generally provide improved bioavailability and reduced toxicity. In this study, Lycium barbarum polysaccharide-stabilized selenium nanoparticles were prepared under mild conditions, characterized, and evaluated for antibacterial, antibiofilm, and antidiarrhoeal activities. The optimized nanoparticles exhibited a hydrodynamic diameter of 304.4 ± 32.9 nm, a polydispersity index of 0.369 ± 0.05, and a zeta potential of −20.8 ± 1.5 mV, indicating good colloidal stability. Scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy supported the structural assignment of spherical elemental selenium particles with a polysaccharide-rich surface layer. In vitro assays showed concentration-dependent inhibition of Escherichia coli, with minimum inhibitory and minimum bactericidal concentrations of 100 and 200 μg Se/mL, respectively. Biofilm formation was also markedly reduced, and scanning electron microscopy demonstrated severe bacterial surface damage after treatment. In a KM mouse model of Escherichia coli-induced diarrhea, oral administration of the nanoparticles significantly lowered diarrhea scores, improved body weight recovery, and alleviated intestinal mucosal injury compared with untreated infected mice. Major organs showed no obvious histopathological abnormalities under the experimental conditions. Overall, these findings identify Lycium barbarum polysaccharide-stabilized selenium nanoparticles as a promising selenium-based nanomaterial for controlling bacterial diarrhea and protecting intestinal health. These results provide a practical foundation for future mechanistic, pharmacokinetic, microbiological, and translational studies aimed at broader intestinal applications. Full article

Enzyme immobilisation within Metal–organic Frameworks (MOFs) provides a promising strategy for improving enzyme dispersion and local environment control, although the resulting performance depends strongly on the host materials, enzyme type and immobilisation conditions. Conventional in situ biomimetic mineralisation typically produces enzyme–MOF composites (enzyme@MOFs) with irregular morphologies, broad particle size distributions and aggregation, which can compromise catalytic performance and reproducibility. This study presents a flow-based microfluidic biomimetic mineralisation strategy for preparing horseradish peroxidase-encapsulated ZnBDC-NH₂ MOF composites. A flow-focusing microfluidic chip containing multiple rectangular baffle structures was designed to enhance transverse mixing, extend the effective residence time, and mitigate clogging during particle formation. Under the selected conditions, homogeneous HRP@ZnBDC-NH₂ particles with an average hydrodynamic diameter of 868.5 nm and a polydispersity index of 0.266 were obtained. The homogeneous HRP@ZnBDC-NH₂ showed an encapsulation efficiency of 56.17% and a loading content of 1.49%. Michaelis–Menten analysis gave a Km value of 52.49 μM for HRP@ZnBDC-NH₂, suggesting improved apparent substrate affinity compared with the corresponding bulk-synthesised sample. The results support the use of baffle-structured microfluidics as a controllable platform for enzyme@MOF synthesis, while further studies on enzyme leaching, reusability, long-term stability and extended chip operation are required to evaluate its operational robustness. Full article

Background/Objectives: Breast cancer remains one of the most prevalent malignancies worldwide, highlighting the need for safer and more effective therapeutic strategies. Curcumin has shown considerable anticancer potential; however, its clinical application is limited by poor aqueous solubility and low skin permeability. Methods: Therefore, a curcumin-loaded microemulsion (CUR-ME) was developed and optimized using a Box–Behnken design, followed by incorporation into a Carbopol 934 gel for topical breast cancer therapy. Results: The optimized formulation exhibited a particle size of 177.4 nm, a polydispersity index of 0.1309, and a zeta potential of −4.45 mV, indicating favorable physicochemical characteristics. CUR-ME demonstrated superior dose-dependent cytotoxicity against MCF-7 breast cancer cells, with a lower IC₅₀ 8.89 µg/mL than free curcumin IC₅₀ 9.83 µg/mL. Furthermore, Hoechst 33342 staining and the DCFDA assay confirmed enhanced apoptosis and intracellular reactive oxygen species generation in CUR-ME-treated cells, indicating improved cellular uptake and anticancer activity. Rheological and texture profile analyses demonstrated suitable viscosity, firmness, and spreadability for topical application. In vitro drug release revealed sustained release from the CUR-ME gel, achieved through the polymeric gel matrix, which increased viscosity, entrapped microemulsion droplets, and acted as a diffusion barrier to prolong drug retention and release. Confocal laser scanning microscopy further confirmed enhanced skin penetration of CUR-ME. Conclusions: Collectively, these findings demonstrate that the developed CUR-ME gel is a promising topical drug delivery system with sustained release, improved skin retention, and enhanced therapeutic potential for breast cancer management. Full article

Background: Nucleic acid vaccines adjuvanted with lipid nanoparticles (LNPs) are a simple and effective means of protection against infectious diseases through the delivery of antigen(s) that elicit(s) specific immunity. DNA vaccines are not commercially available for poultry mainly due to low protective efficacy and the associated production cost. Methods: We introduced here a novel nanoadjuvant system (namely, QTAP) comprising DOTAP and Quil-A for efficient delivery of plasmid DNA (pDNA) constructs into cells and boosting immune responses of chickens. Variable QTAP-pDNA-LNPs formulas were investigated for their physicochemical characteristics, cellular transfection, and in vivo efficacy in a vaccine/challenge model using pDNA encoding both S and N proteins of avian Infectious Bronchitis Virus (IBV). Results: Under electron microscopy, all LNP formulas were spherical in shape and had an overall size range of 45.4–376.3 nm. The formula with the smallest size had the lowest pDNA encapsulation and the highest polydispersity index (PDI). On the contrary, formulas with larger sizes and lower PDI values encapsulated a higher concentration of plasmid payload. Interestingly, the high-payload vaccine formula was stable at both 25 °C and 4 °C for up to 6 weeks of storage, but its gene expression dropped beyond this point at both temperatures. Following immunization of chickens, all groups were challenged with a virulent IBV. Surprisingly, both formulas were able to reduce the IBV viral shedding, indicating their effectiveness even when low concentrations of pDNA were incorporated in LNPs. However, pre-challenge sera from immunized chicks did not elicit IBV-specific antibodies, compared to birds immunized with a commercial live-attenuated IBV vaccine. Conclusions: This study suggests that the QTAP nanoadjuvant system is a safe and effective adjuvant for DNA immunization in poultry that could also be further developed for commercialization. Full article

Kombucha is a fermented tea beverage and a rich source of bioactive compounds with potential health benefits. This study aimed to evaluate the effects of different tea substrates (green, oolong, and black tea) on fermentation characteristics, bioactive compound profiles, antioxidant activity, and cytotoxicity, and to develop a nanoemulsion system for the encapsulation of kombucha-derived bioactive compounds for food applications. Kombucha was fermented for 15 days and during microbial growth, pH, total acidity, and sugar consumption were monitored. The results showed that green tea kombucha exhibited the lowest pH and highest total acidity, indicating more active fermentation. High-performance liquid chromatography analysis revealed that concentrated green tea kombucha contained higher levels of catechin, caffeine, and selected organic acids, whereas black tea kombucha exhibited the highest epigallocatechin gallate (EGCG) concentration. Among the tested samples, green tea kombucha demonstrated superior antioxidant properties as determined by DPPH, ABTS, and FRAP assays, while exhibiting no significant cytotoxicity in RAW 264.7, Caco-2, and A549 cells. Based on these findings, a nanoemulsion system was developed using concentrated green tea kombucha. The nanoemulsion exhibited an average particle size of 110.03 ± 6.2 nm, a polydispersity index of 0.28 ± 0.01, and a zeta potential of +32.5 ± 0.5 mV. Furthermore, the nanoemulsion maintained acceptable physicochemical stability during 6 months of storage at 4 °C, remaining within the nanoscale range with only minor changes in PDI and zeta potential. The encapsulation efficiency reached 91.66 ± 2.29%, and the system demonstrated a biphasic release profile with an initial burst followed by sustained release. Cellular uptake studies confirmed efficient internalization of the nanoemulsion in all tested cell lines. These findings highlight the potential of green tea kombucha as a functional food ingredient and demonstrate the feasibility of nanoemulsion-based systems for the encapsulation and cellular internalization of kombucha-derived bioactive compounds. This study provides a promising strategy for the development of value-added fermented beverages and functional food products. Full article

Background: Taurine is a bioactive amino acid that has great potential for wound healing, but it struggles with poor skin penetration and quick clearance. This study aimed to develop taurine-loaded nanoliposomes (Nlp-Tau) to enable sustained local delivery and improve effectiveness. Methods: Nlp-Tau were prepared using thin-film hydration. We characterized them for size, charge, shape, encapsulation efficiency (EE%), loading efficiency (LE%), and in vitro release. Also, its biocompatibility on human foreskin fibroblasts (HFF) with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assay) has been assessed. In vitro wound healing potential was further evaluated using a scratch assay. Results: Optimized Nlp-Tau showed favorable properties, including an average hydrodynamic diameter of about 282 nm, a polydispersity index of 0.2, a strong negative zeta potential of −31.3 mV, and a spherical shape. However, transmission electron microscopy (TEM) images revealed diameters of about 142 nm and 194 nm for the drug-free and taurine-loaded particles, respectively. Additionally, EE% and LE% were 20% and 2.5%, respectively. In vitro release in PBS (pH 7.4) followed Higuchi kinetics, showing sustained release over 72 h. Nlp-Tau displayed excellent biocompatibility, with HFF viability significantly higher than other groups at concentrations up to 7 mg/mL. Importantly, in the scratch assay, Nlp-Tau treatment resulted in just 6.8% of the wound area remaining after 48 h, which outperformed free taurine at 10.7%. Conclusions: The Nlp-Tau system we developed offers a stable, biocompatible, and effective delivery method for sustained taurine release. It demonstrates greatly improved in vitro wound closure and shows strong potential for future wound care applications. Full article

The production of polymeric nanoparticles using microfluidic systems holds great potential for controlled drug delivery applications. In this study, the effects of flow parameters and surfactant properties on the characteristics of PLGA (Poly (lactic-co-glycolic acid)) nanoparticles were systematically investigated. First, the total flow rate (TFR) and flow rate ratio (FRR) were optimized to ensure stable droplet formation. Subsequently, the effects of different surfactant types (anionic, cationic, and nonionic) and their varying concentrations were evaluated. Using the selected parameters, capsaicin-loaded PLGA nanoparticles were successfully produced. The particles were prepared using a microfluidic platform, and the organic phase was subsequently removed via solvent evaporation. The resulting formulations were comprehensively characterized in terms of particle size, polydispersity index (PDI), zeta potential, and encapsulation efficiency (%EE). Additionally, the in vitro release profiles and cytotoxicity of capsaicin-loaded nanoparticles were evaluated. This study aimed to elucidate the decisive role of surfactant parameters in the microfluidic production of PLGA nanoparticles and to contribute to the development of optimized and reproducible formulations. Full article

Background: Due to the serious side effects and the resistant phenotype acquired by tumors, cisplatin has limited clinical efficacy. The current study aims to investigate the potential of disulfide-bridged phthalocyanines to make breast cancer cells (MCF-7) more sensitive to cisplatin. For this purpose, a novel disulfide-bridged dimeric phthalocyanine complex with a therapeutically active wavelength absorbance value that is activatable in cancer cells was synthesized and encapsulated in liposome nanoparticles. Methods: The synthesized phthalocyanine was characterized using FTIR, UV–visible, and MALDI-TOF-MS techniques; liposome nanoparticles containing the synthesized phthalocyanine were characterized using a particle size analyzer and were tested on MCF-7 breast cancer cell lines using MTT and flow cytometric assays. Results: The results have illustrated that GSH cleavages disulfide bonds of the synthesized disulfide-bridged dimeric phthalocyanine complex with quite favorable characteristics for photodynamic therapy, such as a therapeutically active wavelength absorbance value (685 nm), and disulfide-bridged phthalocyanine (ASG20)-containing liposome nanoparticles have quite favorable characteristics (average size of 167.6 nm and polydispersity index of 0.108) for biomedical applications. As evidenced by MTT and flow cytometric assays, by causing extra decreases in the viability of breast cancer cells (p < 0.01), pre-treatment of the breast cancer cells with photodynamic therapy using the activatable liposome nanoparticles significantly (p < 0.01) enhanced the anticancer activity of cisplatin in high and low doses. Conclusions: In conclusion, the activatable liposome nanoparticles containing disulfide-bridged dimeric phthalocyanine complexes can enable much more effective cisplatin-based therapies for breast cancer by overcoming the handicaps of cisplatin, drug resistance (by decreasing intracellular GSH levels), and serious side effects (by enabling the usage of lower doses of cisplatin in chemotherapy). Full article

Background/Objectives: Tick infestations represent a major economic problem for livestock farming due to the hematophagous nature of these parasites and their crucial role as vectors of pathogens. The prolonged use of synthetic chemical ixodicides has led to resistance, prompting the search for alternative tick-control strategies. In this study, piperine-loaded polymeric nanoparticles were successfully developed using Eudragit^® L100-55 (NP_Pip_1) and Eudragit^® RLPO (NP_Pip_2) polymers, which were physicochemical characterized and evaluated against Rhipicephalus microplus and Amblyomma mixtum larvae resistant to conventional treatments. Methods/Results: NP_Pip_1 and NP_Pip_2 exhibited mean particle sizes of 107.30 ± 6.34 nm and 101.00 ± 1.51 nm, polydispersity index (PDI) values of 0.08 ± 0.02 and 0.05 ± 0.03, ζ potentials of −5.78 ± 2.14 and 32.7 ± 0.74 mV and encapsulation percentages (%E) of 17.44 ± 1.56 and 1.43 ± 0.11. The encapsulation efficiencies (%EE) were 69.76 ± 6.25% and 37.40 ± 2.89%, respectively. Free piperine showed LC₅₀ and LC₉₀ values of 1822.25 and 5981.74 µg/mL against R. microplus, and 1904.18 and 6213.28 µg/mL against A. mixtum. In contrast, NP_Pip_1 reduced LC₅₀ and LC₉₀ values by 1.83- and 2.2-fold against R. microplus and by 1.61- and 1.44-fold against A. mixtum, indicating improved ixodicidal activity compared with free piperine. NP_Pip_2 showed smaller reductions in LC₅₀ and LC₉₀ of 1.34- and 1.33-fold against R. microplus and 1.43- and 1.41-fold against A. mixtum. Conclusions: These results demonstrate that incorporating piperine into polymeric nanoparticles significantly improves its ixodicidal activity against resistant tick larvae, positioning this platform as a promising strategy for the development of alternative treatments against ticks resistant to conventional treatments. Full article

Ellagic acid (EA) possesses various biological activities, including anti-inflammatory, whitening, and antioxidant properties. Its practical application is limited by poor aqueous solubility and susceptibility to degradation. To overcome these limitations, this study prepared EA liposomes using the thin-film hydration–ultrasonication method, followed by surface modification with low-molecular-weight chitosan (LM-CS) and medium-molecular-weight chitosan (MM-CS), yielding EA liposomes modified with LM-CS (EA-L-LC) and MM-CS (EA-L-MC), respectively. The formulation and preparation process were optimized using a Box–Behnken design combined with response surface methodology. Under optimal conditions, the mean particle size (MPS), polydispersity index (PDI), Zeta-potential, and encapsulation efficiency (EE) of the different liposomes (unmodified EA-L, EA-L-LC, and EA-L-MC) were determined. Morphological observation and functional group characterization were conducted via transmission electron microscopy (TEM) and Fourier-transform infrared spectroscopy (FTIR), respectively. The stability of the various liposomes was compared under different environmental conditions, and their stability and the released amount of EA were evaluated during in vitro digestion. The in vitro antioxidant activity and tyrosinase inhibitory effects of the different liposomes were investigated. After process optimization, the encapsulation efficiency of EA liposomes was effectively enhanced following modification with chitosan of different molecular weights. TEM and FTIR results confirmed that EA was effectively encapsulated, and chitosan was successfully coated onto the outer layer of the liposomes. Compared to unmodified EA liposomes (EA-L), the chitosan-modified liposomes (EA-L-LC and EA-L-MC) exhibited enhanced in vitro antioxidant activity and sustained, slow-release tyrosinase inhibitory effects, along with superior stability across multiple conditions. In vitro digestion experiments demonstrated that EA-L-MC and EA-L-LC achieved slower release rates in simulated gastric fluid compared to EA-L, thereby improving the digestive stability of EA. Full article

Here, we report a facile, reproducible, fully aqueous route to fabricate citric acid–crosslinked poly(vinyl alcohol) (PVA) composite hydrogels incorporating polyaniline nanoparticles (PANI-NP) of ca. 200 nm mean diameter and polydispersity index (PDI) below 0.2, synthesized directly in water. Nanocomposites incorporating 2, 3, and 5% w/w PANI-NP were thoroughly characterized in terms of thickness (obtaining materials of approximately 500 µm), morphology, spectroscopic and thermal properties, surface properties, swelling behavior, and nanomechanical behavior assessed by atomic force microscopy (AFM) operating in Peak Force Quantitative Nanomechanical Mapping (PF-QNM) mode. Incorporation of PANI-NP progressively increased the elastic modulus of the composites (from 794 MPa for neat PVA to values exceeding several GPa at 3–5% w/w loading) and modified swelling capacity to values as low as 140% (from 247% for neat PVA), reflecting nanoscale interfacial interactions. Notably, the hydrogel composites exhibited significant photothermal activity under low-power near-infrared (NIR) LED irradiation (850 nm, 90 mW cm⁻²), achieving temperature increases of up to 13.7 °C even at low PANI-NP loadings, with a stable and reproducible response across multiple heating–cooling cycles. Overall, this work establishes a straightforward, water-based fabrication platform for structurally stable, photothermally active nanocomposites with promising potential in light-responsive smart material applications. Full article

Background/Objectives: Micro- and nano-scale hydrogels (microgels and nanogels) have attracted increasing attention as carriers for drug delivery due to their high-water content, responsiveness to external stimuli, tunable properties, and versatility. In this work, gelatin methacryloyl (GelMA) with a medium degree of methacryloylation (DoM ca. 60%) was ad hoc synthesized as a constituent material for nanogel production. For the first time in the literature, GelMA-based nanogels (nanoGelMA) were developed through an optimized two-step desolvation method combined with photo-crosslinking. Methods: The influence of key process parameters, including the pH, volume of desolvating agent, photo-initiator concentration, and UV exposure time, was systematically investigated to identify optimal conditions for nanoGelMA preparation. To assess its potential as a drug delivery nanocarrier, the nanoGelMA was loaded with ibuprofen (IBU) as a model anti-inflammatory drug via in situ encapsulation during nanogel preparation. Results: The formulated nanoGelMA exhibited an average hydrodynamic diameter (d) of ca. 250 nm, a polydispersity index of 0.2, and a production yield of approximately 30%. The nanogels demonstrated stability in water and in phosphate buffer at pH 5 over 96 h, while exhibiting significant swelling in physiological-like conditions and enzymatic degradation (d of ca. 421 ± 91 nm and 609 ± 182 nm at 96 h, respectively). The cytocompatibility evaluation demonstrated high cell viability (86–96%) of the nanoGelMA at different concentrations (1–5 mg/mL). IBU-loaded nanoGelMA particles were successfully developed via direct drug encapsulation during nanogel formation, achieving a maximum encapsulation efficiency of ca. 30%, and exhibited environment-responsive release, with kinetics modulated by the ionic strength, pH, and enzymatic activity. Conclusions: Overall, the nanoGelMA developed herein represents a promising nanogel platform with great potential for the development of advanced and controlled drug delivery therapies. Full article