Search Results (1,942)

The threat of antimicrobial resistance (AMR) and the need for sustainable disinfectants have spurred interest in natural antimicrobials such as essential oils (EOs). However, their application is limited by volatility, poor water solubility, and cytotoxicity. Herein, we present the development of bio-based core–shell sub-micro-/nanocapsules (NCs) with encapsulated oregano (OO), thyme (TO), eucalyptus (EuO), and tea tree (TTO) oils to enhance antimicrobial (AM) performance and reduce cytotoxicity. NCs were synthesized via a nanoencapsulation method using chemically modified zein or poly(methyl vinyl ether-co-maleic anhydride) (GZA) as shell polymers, with selected EOs encapsulated in their core (encapsulation efficacy > 98%). Chemical modification of zein with vanillin (VA) and GZA with either dodecyl amine (DDA) or 3-(glycidyloxypropyl)trimethoxysilane (EPTMS) resulted in improvement in particle size distributions, polydispersity indices (PDIs) of synthesized NCs, and in the stability of the NC-dispersions in water. Antibacterial testing against Staphylococcus aureus and cytotoxicity assays showed that encapsulation significantly reduced toxicity while preserving their antibacterial activity. Among the formulations, GZA-based NCs modified with EPTMS provided the best balance between safety and efficacy. Despite this, life cycle assessment revealed that zein-based NCs were more environmentally sustainable due to lower energy use and material impact. Overall, the approach offers a promising strategy for developing sustainable, effective, and safe EO-based antibacterial agents for AM applications. Full article

Dextrin-based nanosponges (D-NS) are promising candidates for oral drug delivery due to their biocompatibility, mucoadhesive properties, and tunable swelling behavior. In this study, pH-sensitive nanosponges were synthesized using β-cyclodextrin (β-CD), GluciDex^®2 (GLU2), and KLEPTOSE^® Linecaps (LC) as building blocks, crosslinked with pyromellitic dianhydride (PMDA) and citric acid (CA). The nanosponges were mechanically size-reduced via homogenization and ball milling, and characterized by FTIR, TGA, dynamic light scattering (DLS), and zeta potential measurements. Swelling kinetics, cross-linking density (determined using Flory–Rehner theory), rheological behavior, and mucoadhesion were evaluated under simulated gastric and intestinal conditions. The β-CD:PMDA 1:4 NS was selected for drug studies due to its optimal balance of structural stability, swelling capacity (~863% at pH 6.8), and highest apomorphine (APO) loading (8.23%) with 90.58% encapsulation efficiency. All nanosuspensions showed favorable polydispersity index values (0.11–0.30), homogeneous size distribution, and stable zeta potentials, confirming suspension stability. Storage at 4 °C for six months revealed no changes in physicochemical properties or apomorphine (APO) degradation, indicating protection by the nanosponge matrix. D-NS exhibited tunable swelling, pH-responsive behavior, and mucoadhesive properties, with nanoparticle–mucin interactions quantified by the rheological synergism parameter (∆G′ = 53.45, ∆G″ = −36.26 at pH 6.8). In vitro release studies demonstrated slow, sustained release of APO from D-NS in simulated intestinal fluid compared to free drug diffusion, highlighting the potential of D-NS as pH-responsive, mucoadhesive carriers with controlled drug release and defined nanoparticle–mucin interactions. Full article

Background: Self-amplifying mRNA (sa-mRNA) represents a promising platform for vaccines and gene therapies, offering sustained protein expression at low doses through self-replication. For vaccines targeting respiratory pathogens, pulmonary delivery of sa-mRNA lipid nanoparticles (LNPs) is particularly advantageous, enabling direct delivery to the infection site and induction of mucosal immunity. Objective: In this study, we evaluated the stability of sa-mRNA–LNPs under refrigerated and frozen conditions and developed a dry powder formulation suitable for inhalation, produced by freeze-drying followed by cryomilling with leucine. Methods: sa-mRNA–LNPs formulated in HEPES buffer with 20% (w/v) sucrose were stored for up to 8 weeks as liquid or freeze-dried samples at various temperatures (−80 °C, −20 °C, 4 °C, and 20 °C). Biological stability was assessed by transfection efficiency in HeLa cells, while physical stability was characterized by encapsulation efficiency, zeta potential, particle size, and polydispersity index. Results: Liquid formulations remained stable for at least 8 weeks at −80 °C and −20 °C but rapidly lost stability at 4 °C and 20 °C. Freeze-drying effectively preserved sa-mRNA–LNP functionality and structural integrity for up to 8 weeks at 4 °C, with only minor structural changes. Subsequent cryomilling in the presence of 4 wt-% leucine produced a respirable dry powder while retaining approximately 60% of the original sa-mRNA–LNP functionality. Although cryomilling induced some structural alterations, the remaining functional fraction remained stable during storage. The resulting powders displayed favorable aerosol performance for deep lung delivery, as demonstrated by cascade impaction (MMAD = 4.13 ± 0.26 µm). Conclusions: In conclusion, freeze-drying effectively preserved sa-mRNA–LNP integrity at 4 °C, whereas cryomilling with leucine produced a respirable dry powder suitable for pulmonary delivery, providing a foundation for globally accessible, needle-free sa-mRNA vaccines against respiratory diseases. Full article

Introduction: Magnetic nanoparticles are widely investigated as multifunctional platforms for drug delivery and theranostic applications, yet their biomedical implementation is hindered by aggregation, limited colloidal stability, and insufficient biocompatibility. Hybrid biopolymer coatings can mitigate these issues while supporting drug incorporation. Aim: This study aimed to develop casein–pullulan-coated Fe₃O₄ nanocomposites loaded with xanthohumol, enhancing stability and enabling controlled release for potential theranostic use. Methods: Fe₃O₄ nanoparticles were synthesized through co-precipitation and incorporated into a casein–pullulan matrix formed via polymer complexation and glutaraldehyde crosslinking. A 3² full factorial design evaluated the influence of casein:pullulan ratio and crosslinker concentration on physicochemical performance. Nanocomposites were characterized for size, zeta potential, morphology, composition, and stability, while drug loading, encapsulation efficiency, and release profiles were determined spectrophotometrically. Molecular docking was performed to examine casein–pullulan interactions. Results: Uncoated Fe₃O₄ nanoparticles aggregated extensively, displaying mean sizes of ~292 nm, zeta potential of +80.95 mV and high polydispersity (PDI above 0.2). Incorporation into the biopolymer matrix improved colloidal stability, yielding particles of ~185 nm with zeta potentials near –35 mV. TEM and SEM confirmed spherical morphology and uniform magnetic core incorporation. The optimal formulation, consisting of a 1:1 casein:pullulan ratio with 1% glutaraldehyde, achieved 5.7% drug loading, 68% encapsulation efficiency, and sustained release of xanthohumol up to 84% over 120 h, fitting Fickian diffusion (Korsmeyer–Peppas R² = 0.9877, n = 0.43). Conclusions: Casein–pullulan hybrid coatings significantly enhance Fe₃O₄ nanoparticle stability and enable controlled release of xanthohumol, presenting a promising platform for future targeted drug delivery and theranostic applications. Full article

Glioblastoma (GBM) is a highly aggressive brain tumor characterized by invasive growth, intrinsic drug resistance, and the presence of the blood–brain barrier. All of these features make treatment extremely challenging and underscore the need for developing effective combination strategies and advanced drug delivery systems. This study aimed to develop a bovine serum albumin (BSA) nanoparticle (NP)-based delivery system to overcome the poor bioavailability and pharmacokinetic limitations of two potent anti-tumor agents, all-trans retinoic acid (ATRA) and curcumin (CURC), and to evaluate their antitumor activity in U87-MG GBM cells. Drug-free and ATRA/CURC-loaded BSA-NPs were synthesized using an optimized desolvation method and characterized in terms of particle size, polydispersity index, morphology, drug encapsulation efficiency, and release behavior. The cytotoxic, anti-migratory, and pro-apoptotic effects of the NPs on U87-MG GBM cells were assessed using real-time proliferation and migration assays and Annexin V/PI staining followed by flow cytometry. Collectively, the findings indicated that the co-delivery of ATRA and CURC using BSA-NPs showed enhanced antiproliferative, antimigratory, and pro-apoptotic effects. With its controlled release profile, high loading capacity, and favorable nanoscale dimensions, the ATRA-CURC-BSA–NP system represents a promising nanoplatform for GBM therapy that warrants further in vivo investigation. To the best of our knowledge, this is the first study demonstrating the inhibition of glioblastoma cell growth through the co-delivery of all-trans retinoic acid and curcumin using a bovine serum albumin-based nanoparticle system. Full article

Background: Nanotechnology provides innovative strategies to enhance drug delivery and therapeutic efficacy through advanced nanocarrier systems. Objectives: This study aimed to develop and optimize a nanostructured lipid carrier (NLC) co-encapsulating curcumin (CUR) and resveratrol (RESV) using a fractional factorial design to develop a topical formulation with antioxidant and anti-inflammatory properties. Methods: NLCs were produced via hot emulsification followed by high-pressure homogenization, and their physicochemical characteristics, drug content, stability, release profile, antioxidant activity, skin delivery, and cellular compatibility were evaluated. Results: The optimized formulation exhibited an average particle size of approximately 300 nm, a polydispersity index below 0.3, and high drug loading for both compounds. Stability studies over 90 days revealed no significant changes in physicochemical parameters, confirming the formulation’s robustness. In vitro release assays demonstrated sustained release of both actives, with 58.6 ± 2.9% of CUR and 97 ± 3% of RESV released after 72 h. Antioxidant activity, assessed by the DPPH and ABTS assays, showed concentration-dependent radical-scavenging effects, indicating antioxidant potential. Skin permeation/retention experiments using porcine skin showed enhanced retention of CUR and RESV within the tissue, with no detectable permeation, indicating suitability for topical delivery. In addition, in vitro cell assays using human keratinocytes showed concentration-dependent responses and acceptable cellular compatibility. Conclusions: Overall, this study demonstrates the successful application of nanotechnology and experimental design to develop stable and efficient lipid-based nanocarriers containing natural polyphenol for topical therapy targeting oxidative and inflammatory skin disorders. Full article

Green technologies are actively being used to produce nanosized zinc oxide, which is in demand for water purification processes to remove pollutants. Despite the success of the green synthesis of ZnO nanoparticles, no scientific approach exists for selecting plant extracts to produce nanoparticles with the desired properties. This study shows that the antioxidant activity of the plant extracts used is a key parameter influencing the properties of the resulting ZnO nanoparticles. This conclusion is based on the results of nanoparticle synthesis with the use of various plant extracts. The antioxidant activity of the extracts increases in the following order: plum–gooseberry–black currant–strawberry–sea buckthorn. The synthesized ZnO nanoparticles were characterized by UV–visible spectroscopy, transmission electron microscopy, and energy-dispersive X-ray spectroscopy. The catalytic properties of ZnO nanoparticles were tested under the degradation of a synthetic methylene blue dye after exposure to UV light. We found that with an increase in the AOA of plant extracts, the size of the nanoparticles decreases, while their photocatalytic activity increases. The smallest (d = 13 nm), most uniform in size (polydispersity index 0.1), and most catalytically active ZnO nanoparticles with a small band gap (2.85 eV) were obtained using the sea buckthorn extract with the highest AOA, pH 10 of the reaction mixture and 0.1 M Zn(CH₃COO)₂∙2H₂O as a precursor salt. ZnO nanoparticles synthesized in the sea buckthorn extract demonstrated the highest dye photodegradation efficiency (96.4%) compared with other nanoparticles. The established patterns demonstrate the “antioxidant activity–size–catalytic activity” triad can be considered as a practical guide for obtaining ZnO nanoparticles of a given size and with given properties for environmental remediation applications. Full article

Saccharomyces cerevisiae was cultured under the influence of static magnetic fields (SMFs) to assess their impact on the biosynthesis of silver nanoparticles (AgNPs). Cell-free media derived from SMF-exposed cultures facilitated the formation of AgNPs, with a significant reduction in nanoparticle size observed at an optimal field strength of 7 mT. AgNPs synthesized under SMF conditions exhibited smaller crystalline structures than those produced in control media, as evidenced by dynamic light scattering (DLS) and transmission electron microscopy (TEM) measurements. Over a 75-day period, SMF-exposed AgNPs demonstrated enhanced stability, as determined by DLS and polydispersity index (PDI) assessments. Further analysis through sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Fourier transform infrared spectroscopy (FTIR) suggested the formation of a protein corona on the AgNPs in SMF-treated samples, which likely inhibits agglomeration and enhances long-term stability. These findings indicate that SMF-induced stress in S. cerevisiae triggers the secretion of specific proteins that contribute to the stabilization of AgNPs, providing a novel approach to controlling nanoparticle synthesis and stability through magnetic field exposure. Full article

As a natural flavonoid compound, quercetin possesses excellent antioxidant, anti-inflammatory and anti-atherosclerotic activities. However, the poor water solubility and sensitivity to the environment severely limit the application of quercetin. Initially, quercetin-loaded zein/carboxymethyl chitosan nanoparticles (ZCQ NPs) were prepared using an anti-solvent precipitation method. The fabricated ZCQ NPs exhibited a small particle size and polydispersity index (PDI). The ZCQ NPs had a negative zeta potential with an absolute value of 41.50 ± 1.76 mV. ZCQ NPs could remain highly stable against light, heat and ion strength. In addition, ZCQ NPs maintained good monodispersity and displayed minimal changes in particle size under long-term storage conditions. Additionally, a superior antioxidant capacity of ZCQ NPs was also observed in the free radical and reactive oxygen species (ROS) scavenging study compared to that of free quercetin. All these results of this study suggest that ZCQ NPs could serve as an effective drug delivery system for encapsulating and delivering quercetin. Full article

Brown algae of the Cystoseira genus are recognized as valuable sources of bioactive compounds, including polysaccharides. Within the framework of current restoration efforts regarding damaged Ericaria amentacea populations in the Mediterranean Sea, the valorization of apices derived from ex situ cultivation waste represents a sustainable opportunity for industrial and biomedical applications. In this study, sodium alginate (SA) was extracted from E. amentacea apex by-products using a hydrothermal–alkaline method and subsequently chemically characterized. FTIR analysis showed O-H, C-H, and COO- stretching compatible with commercial alginates, while 1H-NMR spectroscopy indicated high β-D-mannuronic acid content, with an M/G ratio of 2.33. The extracted SA displayed a molecular weight of 1 × 10⁴ g/mol and a polydispersity index of 3.5. The bioactive properties of the SA extract were investigated in chemico and in vitro. SA exhibited remarkable antioxidant activity, showing significant DPPH and nitric oxide-radical-scavenging capacity. Furthermore, SA demonstrated a strong anti-inflammatory effect in LPS-stimulated macrophages through modulation of several inflammatory mediators (i.e., IL-6, IL-8/CXCL5, MCP-1, and TNF-α). In particular, SA promoted a striking iNOS gene expression inhibition, which, paired with its direct NO-scavenging ability, paves the way for future pharmacological use of E. amentacea derivatives, particularly if sustainably obtained from restoration activity waste. Full article

Spodoptera frugiperda (fall armyworm) is a polyphagous pest with widespread resistance to synthetic insecticides, while essential oils (EOs) and biological control agents, such as the parasitoid Trichogramma pretiosum, represent promising strategies in integrated pest management (IPM) programs. This study evaluated the toxicity of Eugenia uniflora EO, popularly known as pitanga EO, and nanoemulsion (NEO) to S. frugiperda and the selectivity of the NEO to T. pretiosum. The EO of E. uniflora was characterized by GC-MS/DIC and then diluted in water and Tween 80^® for bioassays to estimate the LC₅₀ against S. frugiperda in Potter’s tower. The NEOs were produced by high-shear dispersion using an Ultra-Turrax and characterized for thermal stability, particle size, polydispersity index (PDI), zeta potential (ζ), temporal stability, and morphology. The NEO was diluted to the LC₅₀ (36.05 mg/mL) in 1% Tween 80^® solution and tested for toxicity to S. frugiperda and to the parasitoid. The majority compounds in the EO from E. uniflora were curzerene (34.07%), selina-1,3,7(11)-trien-8-one (10.51%), germacrene B (9.51%) and germacrene D (5.03%). The NEO stored at 25 °C remains stable for up to 30 days after preparation. In addition, the NEO showed a particle size of 283.2 nm, a PDI of 0.289, and a zeta potential (ζ) of −23.2 mV. The E. uniflora EO and NEO at a concentration of 36.05 mg/mL were toxic to S. frugiperda (36% probability of survival). Furthermore, NEO was selective for T. pretiosum in its immature stages. The NEO proved to be stable, effective, and selective, indicating potential for IPM. However, validation under semi-field and field conditions is still necessary. Full article

Background: Drug delivery against ciprofloxacin-resistant microbial strains is one of the most challenging areas of research in the pharmaceutical industry. The broad-spectrum antibiotic ciprofloxacin often faces challenges due to its poor bioavailability; thus, the activity of this drug is generally compromised against resistant strains. Traditional drug delivery systems, such as liposomes, are utilized to address this issue; however, niosomes have surfaced as a promising successor to their liposomal counterparts due to their superior attributes, such as enhanced stability and reduced toxicity. However, owing to environmental and toxicological concerns over commonly used chemical surfactants in niosomes, there is a pressing need to explore greener and safer alternatives. This study is focused on the application of sophorolipids (SLs), a biosurfactant that is synthesized by the yeast Starmerella bombicola, as a vesicular assembly for ciprofloxacin encapsulation. Methods: The SL-based niosomal formulation was characterized for particle size, zeta potential, and polydispersity index (PDI), while transmission electron microscopy (TEM) was employed to determine the morphology of niosomes. Agar well diffusion, broth dilution, and biofilm inhibition assays were performed to assess efficacy. Results: The niosomal formulations were successfully prepared; among them, the (+)vely charged formulation exhibited a more organized morphology, and their size and zeta potential values were found to be around ~371 nm and 63 mV for the blank niosomes (without the loaded drug) and ~269 nm and 51 mV for the ciprofloxacin-loaded niosomes. The minimum inhibitory concentration and biofilm inhibitory concentration against the MRSA strain were 5 µg/mL and 25 µg/mL, respectively, for the ciprofloxacin-loaded, (+)vely charged SL niosomes—for free ciprofloxacin these values were 40 µg/mL and 100 µg/mL—presenting remarkable potential for biofilm inhibition. Conclusion: This study highlights the promising therapeutic potential of SL-based ciprofloxacin-loaded niosomes against the emerging health threat of the MRSA strain. Full article

Background: Diabetic nephropathy (DN) is largely driven by transforming growth factor-β1 (TGF-β1)-mediated fibrosis. Clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) ribonucleoprotein (RNP) complexes offer precise gene disruption, yet effective non-viral delivery remains a challenge. This study developed cationic lipid-based hybrid nanostructured lipid carriers (NLCs) for intracellular delivery of TGFB1-targeting RNP as an early-stage platform for DN gene modulation. Methods: A single-guide RNA (sgRNA) targeting human TGFB1 was assembled with Cas9 protein (1:1 and 1:2 molar ratios). Hybrid NLCs comprising squalene, glyceryl trimyristate, and the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) were formulated via optimized emulsification–sonication to achieve sub-100 nm particles. Physicochemical properties, including polydispersity index (PDI), were assessed via dynamic light scattering (DLS), while silencing efficacy in HEK293T cells was quantified using quantitative reverse transcription PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Results: Optimized NLCs achieved hydrodynamic diameters of 65–99 nm (PDI < 0.5) with successful RNP complexation. The 1:2 Cas9:sgRNA formulation produced the strongest gene-editing response, reducing TGFB1 mRNA by 67% (p < 0.01) compared with 39% for the 1:1 ratio. This translated to a significant reduction in TGF-β1 protein (p < 0.05) within 24 h. Conclusions: DOTAP-based hybrid NLCs enable efficient delivery of CRISPR–Cas9 RNP and achieve significant suppression of TGFB1 expression at both transcriptional and protein levels. These findings establish a promising non-viral platform for upstream modulation of profibrotic signaling in DN and support further evaluation in kidney-derived cells and in vivo renal models. Full article

Background: Aristolochia clematitis L. (AC), a plant with diverse traditional uses, has gained increasing scientific interest due to its rich content of bioactive compounds such as flavonoids and polyphenols. However, its systemic use is limited by the presence of aristolochic acids, which are known for their nephrotoxic and carcinogenic potential. Methods: In this context, the present study investigates the therapeutic potential of A. clematitis extract by encapsulating it in liposomes with the aim of enhancing its topical efficacy. Results: The extract was characterized in terms of its flavonoid content (67.23 ± 0.33 mg QE/g DW (quercetin/dry plant material)) and polyphenols expressed as gallic acid equivalents (64.38 ± 0.16 mg GAE/g DW), as well as its antioxidant capacity using the reagents 1,1-diphenyl-2-picrylhydrazyl (DPPH − IC₅₀ = 0.1619 mg/mL extract) and diammonium 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS − IC₅₀ = 205.57 μg/mL extract). Four types of liposomes were synthesized (two loaded with extract and two empty), and their characterization was performed using Atomic Force Microscopy (AFM), Dynamic Light Scattering (DLS), Zeta Potential, polydispersity index, and in vitro release studies. Conclusions: The results demonstrated a high entrapment efficiency (over 82%), good stability over 30 days, and controlled release of flavonoids. Microbiological studies revealed relevant antimicrobial activity against Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, and Pseudomonas aeruginosa strains. The evaluation on HaCaT skin-derived cells (at 10–100 µg/mL) proved that the samples displayed good overall tolerability, slightly decreasing cell viability (the most statistically significant being associated with AC treatment) and showing no structural, nuclear, or mitochondrial morphological changes. Full article

Background: 5-Azacytidine (5-Aza) is a clinically important DNMT inhibitor with the potential to modulate cardiac remodeling by epigenetically reprogramming human cardiac fibroblasts (HCFs). However, its clinical utility is limited by rapid hydrolytic degradation. Nanoparticle (NP) encapsulation offers a strategy to mitigate this instability. This study evaluated the physical and chemical stability of free 5-Aza and 5-Aza-loaded lipid nanoparticles (5-Aza-NP) under different storage temperatures and examined their effects on DNA methylation-related gene expression in HCFs. Methods: Hyaluronic acid-stabilized lipid NPs were prepared using a solvent displacement method. Particle size, polydispersity index (PDI), and zeta potential were monitored over four days at −20 °C, 4 °C, and 30 °C. Chemical stability was assessed using HPLC and first-order kinetic modeling. Functional activity was evaluated by treating HCFs with free 5-Aza or 5-Aza-NP stored for 96 h and measuring DNMT1, DNMT3A, and DNMT3B expression by RT-qPCR. Results: 5-Aza-NP remained physically stable at 4 °C, while −20 °C induced aggregation and 30 °C caused thermal variability. Free 5-Aza degraded rapidly at 30 °C (6.56% remaining at 72 h), whereas 5-Aza-NP preserved 11.54%. Kinetic modeling confirmed first-order degradation, with consistently longer half-lives for the NP formulation. Functionally, 5-Aza–NP preserved its ability to suppress DNMT1 expression following 96 h of storage at 4 °C, whereas free 5-Aza showed reduced activity. In contrast, DNMT3A and DNMT3B levels remained low and unchanged across all treatments. Conclusions: NP encapsulation enhances the physicochemical stability of 5-Aza and preserves its DNMT1-inhibitory activity, while DNMT3A/B remain unaffected. These findings support NP-based delivery as a promising strategy to stabilize labile epigenetic drugs such as 5-Aza. Full article