Search Results (132)

The search for sustainable, economically viable, and effective plant protection strategies against pathogenic bacteria, fungi, and viruses is a major challenge in modern agricultural practices. Chitosan (CS) is an abundant cationic natural biopolymer known for its biocompatibility, low toxicity, and antimicrobial properties. Its potential use in agriculture for pathogen control is a promising alternative to traditional chemical fertilisers and pesticides, which raise concerns regarding public health, environmental protection, and pesticide resistance. This study focused on the preparation of chitosan nanoparticles (CS-NPs) through cross-linking with organic molecules, such as tannic acid (TA). Various formulations were explored for the development of stable nanoscale particles having encapsulation capabilities towards low compounds of varying polarity and with potential agricultural applications relevant to plant health and growth. The solution properties of the NPs were assessed using dynamic and electrophoretic light scattering (DLS and ELS); their morphology was observed through atomic force microscopy (AFM), while analytical ultracentrifugation (AUC) measurements provided insights into their molar mass. Their properties proved to be primarily influenced by the concentration of CS, which significantly affected its intrinsic conformation. Additional structural insights were obtained via infrared and UV–Vis spectroscopic measurements, while detailed fluorescence analysis with the use of three different probes, as model cargo molecules, provided information regarding the hydrophobic and hydrophilic microdomains within the particles. 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

Ulcerative colitis (UC) is a multifactorial disorder, and conventional oral berberine (BBR) suffers from poor colonic targeting. This study aimed to develop a colon-targeted microparticle system (BBR-ES MPs) based on chitosan (CS) and Eudragit S-100 to enhance BBR delivery efficiency and therapeutic efficacy in UC. Methods: BBR-CS nanocarriers were prepared via ionotropic gelation and coated with Eudragit S-100 to form pH/enzyme dual-responsive MPs. Colon-targeting performance was validated through in vitro release assays. SPF-grade male KM mice (Ethics Approval No.: JMSU-2021090301) with dextran sulfate sodium (DSS)-induced UC were divided into normal, model, BBR, and BBR-ES MPs groups. Therapeutic outcomes were evaluated by monitoring body weight, disease activity index (DAI), colon length, histopathology, inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-10), and myeloperoxidase (MPO) activity via ELISA. Gut microbiota diversity was analyzed using 16S rRNA sequencing. Results: BBR-ES MP treatment significantly reduced DAI scores (p < 0.01), restored colon length, downregulated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α; p < 0.05), and upregulated anti-inflammatory IL-10. Microbiota analysis revealed that the Bacteroidetes/Firmicutes ratio, which decreased in the model group, was restored post-treatment, with alpha/beta diversity approaching normal levels. BBR-ES MPs outperformed free BBR at equivalent doses. Conclusion: BBR-ES MPs achieved colon-targeted drug delivery via pH/enzyme dual-responsive mechanisms, effectively alleviating UC inflammation and modulating gut dysbiosis, offering a safe and precise therapeutic strategy for UC management. Full article

The growing demand for natural preservatives in the food industry has highlighted the importance of essential oils (EOs), despite their limitations related to volatility and oxidative instability. This study addresses these challenges by developing pectin-based microcapsules for encapsulating lemon essential oil (LEO) using ultrasound-assisted ionotropic gelation. The EO, extracted from Citrus limon (Eureka variety), exhibited a high limonene content (56.18%) and demonstrated significant antioxidant (DPPH IC50: 28.43 ± 0.14 µg/mL; ABTS IC50: 35.01 ± 0.11 µg/mL) and antifungal activities, particularly against A. niger and Botrytis spp. Encapsulation efficiency improved to 82.3% with ultrasound pretreatment, and SEM imaging confirmed spherical, uniform capsules. When applied to fresh-cut apples, LEO-loaded capsules significantly reduced browning (browning score: 1.2 ± 0.3 vs. 2.8 ± 0.2 in control), microbial load (4.9 ± 0.2 vs. 6.5 ± 0.4 log CFU/g), and weight loss (4.2% vs. 6.4%) after 10 days of storage at 4 °C. These results underscore the potential of ultrasound-enhanced pectin encapsulation for improving EO stability and efficacy in food preservation systems. Full article

Introduction: Many orally administered drugs are either unstable in the acidic environment of the stomach or cause moderate to severe side effects in the upper gastrointestinal tract (GIT). These limitations can reduce therapeutic efficacy, discourage patient compliance, worsen the disease, and even contribute to the risk of cancer development. To overcome these issues, drug release often needs to be modified and targeted to the distal parts of the GIT. This is typically achieved through the use of pH-sensitive polymer coatings or incorporation into polymeric delivery systems. With this in mind, the aim of this project was to design, develop, and characterize gellan gum-based beads for colon-specific prolonged release of mesalazine, with potential application in the chemoprevention and treatment of bowel diseases. Materials and Methods: The dehydrated capsules were characterized using Raman spectroscopy and scanning electron microscopy. The crosslinked gellan gum was additionally evaluated for cytotoxicity. Key parameters such as pH-dependent swelling behavior, drug content, encapsulation efficiency, and drug release in simulated gastrointestinal fluids were also assessed. Furthermore, the behavior of the capsules in the gastrointestinal tract was studied in a rat model to evaluate their in vivo performance. Results: Significant differences in drug release profiles were observed between formulations crosslinked solely with calcium ions and those additionally crosslinked with glutaraldehyde (GA). The incorporation of GA effectively prolonged the release of mesalazine. These findings were further supported by in vivo studies conducted on Wistar rats, where the GA-crosslinked formulation demonstrated a markedly extended release compared to the formulation prepared using only ionotropic gelation. Conclusions: The combination of ionotropic gelation and glutaraldehyde crosslinking in gellan gum-based beads appears to be a promising strategy for achieving colon-specific prolonged release of mesalazine, facilitating targeted delivery to the distal regions of the gastrointestinal tract. Full article

Background/Objectives: Non-small cell lung cancer (NSCLC) constitutes over 84% of all lung cancer cases and is a leading cause of cancer-related mortality globally. Alectinib, a second-generation anaplastic lymphoma kinase (ALK) inhibitor, is effective in ALK-positive NSCLC; however, its clinical potential is hampered by poor aqueous solubility and limited oral bioavailability. This study aimed to develop Alectinib-loaded chitosan–alginate nanoparticles (ACANPs) to enhance its solubility, oral bioavailability, and therapeutic efficacy. Methods: ACANPs were synthesized using a novel combined solid/oil/water (s/o/w) emulsification technique with ionotropic gelation. Characterization was performed using Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), dynamic light scattering (DLS), and zeta potential measurements. A validated high-performance liquid chromatography (HPLC) method quantified the Alectinib. In vitro drug release studies compared free Alectinib with ACANPs. Cytotoxicity against NSCLC cell lines (A549 and H460) was assessed using MTT assays. Pharmacokinetic parameters were evaluated in rats using LC–MS/MS. Results: ACANPs showed a high encapsulation efficiency (~97%), an average particle size of 161 nm, and a positive zeta potential of +21 mV. In vitro release studies revealed a threefold increase in drug release from ACANPs over 48 h compared to free Alectinib. Cytotoxicity assays demonstrated significantly reduced IC₅₀ values for ACANPs. Pharmacokinetic analyses showed an enhanced maximum plasma concentration (C_max) and area under the curve (AUC), indicating a 78% increase in oral bioavailability. Conclusions: ACANPs substantially improved the solubility, cytotoxic efficacy, and oral bioavailability of Alectinib, suggesting their potential as a promising nanocarrier system for enhancing NSCLC treatment outcomes. Full article

This study explores the potential of Vigna mungo gum as a sustainable and innovative natural polymer for developing microbeads for the controlled delivery of vildagliptin, a widely used antidiabetic agent. Unlike conventional natural polymers, Vigna mungo gum offers unique biocompatibility, biodegradability, and an eco-friendly production process, distinguishing it as a superior candidate for drug delivery systems. Microbeads were prepared by combining Vigna mungo gum with sodium alginate and inducing gelation using calcium carbonate. Scanning electron microscopy (SEM) revealed a rough, porous microbead surface, advantageous for drug encapsulation and controlled release. Drug release studies demonstrated sustained release kinetics, highlighting the effectiveness of this formulation. These findings underscore the novelty of Vigna mungo gum as a promising platform for antidiabetic drug delivery, providing a sustainable alternative to existing polymer systems. Full article

Background/Objectives: Alginate nanoparticles (NPs) are commonly synthesised using either an emulsion technique that involves organic solvent use or ionotropic gelation utilising multivalent cations, e.g., Ca⁺². However, the extensive use of organic solvents imposes detrimental effects on the ecosystem, and using multivalent cations as crosslinkers could eventually lead to the leakage of these cations, thus disrupting nanoparticle matrices. Therefore, this study aimed to overcome the limitations of these techniques by eliminating the usage of organic solvents and multivalent cations. Methods: In this research, alginate nanoparticles were synthesised using proton gelation by microfluidic technology through protonating alginate carboxylate groups to crosslink alginate chains through H-bond formation. Results: The prepared acid-gelled alginate nanoparticles demonstrated an MHD circa 200 nm and a PDI of less than 0.4 at pH 0.75. Moreover, 5-FU was successfully encapsulated into acid-gelled alginate nanoparticles and displayed a high EE% of around 30%, comparable to the EE% at high alginate concentration and molecular weight (0.4 H-ALG) achieved by Ca⁺²-crosslinked alginate nanoparticles; however, 5-FU NPs had superior characteristics, i.e., a lower MHD (around 500 nm) and PDI (<0.5). The optimum formula (0.4 H-ALG) was explored at various pH values, i.e., low pH of 4.5 and high pH of 10, and alginate NPs produced by acid gelation demonstrated high stability in terms of MHD and PDI, with slight changes at different pH values, indicating stable crosslinking of alginate matrices prepared by technology compared with Ca⁺²-crosslinked alginate NPs. Conclusions: In conclusion, this research has invented an ecologically friendly approach to producing acid-gelled alginate nanoparticles with superior characteristics compared with the conventional methods, and they could be harnessed as nanocarriers for therapeutics delivery (5-FU). Also, this research offers a promising approach for developing eco-friendly and biocompatible drug carriers. The produced nanoparticles have the potential to enhance drug stability, improve controlled release, and minimise toxic effects, making them suitable for pharmaceutical applications. Full article

Background/Objectives: Bovine mastitis (BM), a prevalent and economically burdensome bacterial infection affecting dairy cattle, poses a significant challenge to the dairy industry. The traditional approach to combating BM, relying heavily on antibiotics, faces growing concerns due to the increasing antibiotic resistance exhibited by pathogens. The objective of this study was to evaluate and determine the antimicrobial and anti-biofilm potential of chitosan nanoparticles (NQo) on S. aureus strains isolated from milk samples obtained from dairy areas in southern Chile from cows diagnosed with BM. Methods: NQo were synthesized using the ionotropic gelation method and thoroughly characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Results: The NQo exhibit a robust positive charge (Z-potential of +55.4 ± 2.5 mV) and an exceptionally small size (20.3 ± 3.2 nm). This unique combination of properties makes NQo particularly well-suited for targeting and interacting with bacterial pathogens. To assess the effectiveness of NQo against BM, we conducted a series of experiments using a Staphylococcus aureus strain isolated from milk samples of cows diagnosed with BM in southern Chile. NQo demonstrated a remarkable ability to inhibit bacterial proliferation and effectively modulate biofilm formation in the S. aureus strains. Furthermore, the performance of NQo in comparison to established antibiotics like ampicillin and gentamicin strongly suggests that these nanoparticles hold immense potential as an attractive alternative for the control, prevention, and/or treatment of BM. Conclusions: NQo exhibit both antimicrobial and antibiofilm activity against a clinically relevant BM pathogen. Further investigations are necessary to develop a hydrogel formulation optimized for effective delivery to the target diseased tissue. Full article

Background/Objectives: Crickets are recognized as an alternative source of chitosan. This study aimed to assess the potential of cricket-derived chitosan as a natural source to develop chitosan nanoparticles (CNPs). Methods: Chitosan were isolated from different cricket species, including Gryllus bimaculatus, Teleogryllus mitratus, and Acheta domesticus. The isolated chitosan were characterized by their functional groups, crystallographic and thermal properties, molecular structure, morphology, water solubility, molecular weight, binding capacity, irritation potential, and cytotoxicity in comparison to commercial shrimp-based chitosan. CNPs were developed through an ionotropic gelation method, followed by the evaluation of particle size, polydispersity index (PDI), and zeta potential. Results: The findings of this study indicate that chitosan can be successfully isolated from the three cricket species, with yields ranging from 4.35% to 5.22% w/w of the dried material. The characteristics of cricket-based chitosan were similar to those of commercial chitosan, except that the cricket-based chitosan displayed a higher crystallinity and a lower molecular weight. Additionally, CPNs were successfully produced from cricket-based chitosan using sodium citrate as a crosslinking agent. All cricket-based chitosan exhibited no irritation or cytotoxicity. Chitosan derived from A. domesticus however was found to be the most suitable to develop CPNs, as it produced the smallest particle size (522.0 ± 12.1 nm) with a comparatively narrow PDI (0.388 ± 0.026) and an acceptable positive zeta potential (34.2 ± 4.4 mV). Conclusions: Cricket-derived chitosan compares favorably with crustacean-derived chitosan and showed potential for a range of applications, including the use as a nanocosmeceutical delivery system in topical and cosmetic formulations. Full article

Olive phenolic compounds like hydroxytyrosol (OH-Tyr), tyrosol (Tyr), and their precursors have different health-promoting properties, mainly based on their strong antioxidant capacity. However, their presence in extra-virgin olive oil (EVOO) is scarce since they are primarily contained in the by-products of oil production, such as olive pomace (OP). The aim of this work was to extract and encapsulate OP phenolic compounds into chitosan–tripolyphosphate nanoparticles (NPs) using an ionotropic gelation lyophilization approach to increase their resistance to environmental and chemical stress. NPs resulted in a monodisperse (PDI: 0.21) population of cationic NPs (ζ-potential: 33 mV, size: 229 nm) with an encapsulation efficiency (EE%), expressed as total phenolic content (TPC) and total OH-Tyr + Tyr content, of 64–65%. Mannitol and maltodextrin DE 19 (MD-19) were evaluated as lyoprotectants to counteract irreversible NP aggregation during lyophilization. The NP powder freeze dried using 0.7% of MD-19 showed the best performance, returning a monodispersed population of particles after rehydration. The antioxidant capacity of the obtained NPs was confirmed both in cell-free assays and in a THP-1 cell model of oxidative stress. This method represents a promising way to deliver health-promoting olive phenols for nutraceutical purposes and, hence, to valorize otherwise wasted by-products. Full article

Chitosan (Ch), a natural polysaccharide, is known for its biocompatibility, biodegradability, and various beneficial properties, including antioxidant and antibacterial activities. The objective of this study is to investigate the functionalization of zinc oxide (ZnO) with chitosan to develop a novel ZnO@Ch adduct for use in cosmetic formulations, specifically as a sun protection agent. The functionalization was achieved through ionotropic gelation, which enhanced the stability and reduced the photocatalytic activity of ZnO, thereby improving its safety profile for skin applications. FTIR spectroscopy confirmed the successful functionalization, while TGA and DSC characterized the thermal properties and stability. The Zeta potential and particle size analyses demonstrated improved stability of ZnO@Ch across various pH levels compared to uncoated ZnO. The structure of the obtained adduct was also confirmed by SEM analysis. The ZnO@Ch adduct exhibited enhanced stability at neutral and slightly alkaline pH values, reduced photocatalytic activity compared to pure ZnO, and had lower cytotoxicity in 3T3 cells compared to pure ZnO, particularly at higher concentrations. The ZnO@Ch adduct provided a higher Sun Protection Factor (SPF) and UVA Protection Factor (UVA-PF) than pure ZnO, indicating enhanced UV protection. The adduct’s ability to provide higher SPF at lower ZnO concentrations offers economic and environmental benefits, aligning with sustainable product design principles. Future studies will focus on optimizing the formulation and testing the efficacy and safety at higher concentrations to fully realize its potential as a natural, eco-friendly sunscreen ingredient. Full article

Background: This study focused on evaluating the physiochemical characteristics and antibacterial activity of Octoprohibitin-encapsulated CNPs (Octoprohibitin-CNPs) against Acinetobacter baumannii. Methods: Octoprohibitin was encapsulated into CNPs via ionotropic gelation with carboxymethyl chitosan (CMC) and low molecular weight chitosan (CS). Octoprohibitin-CNPs were dispersed in phosphate-buffered saline and the release kinetic profile was determined. Then Octoprohibitin-CNPs were examined using field-emission transmission electron microscopy and physicochemical characterization was performed. Antibacterial activity of Octoprohibitin-CNPs against A. baumannii was evaluated. Biofilm inhibition and eradication assays were performed using the crystal violet (CV) staining-based method for biofilm quantification. Results: The average diameter, zeta potential, encapsulation efficiency, and loading capacity of Octoprohibitin-CNPs were 244.5 ± 21.97 nm, +48.57 ± 0.38 mV, and 85.7% and 34.2%, respectively. TEM analysis imaging revealed that Octoprohibitin-CNPs are irregularly shaped, with fewer aggregates than CNPs. Octoprohibitin-CNPs exhibited a biphasic release pattern, characterized by an initial rapid phase followed by a sustained release over time, extending up to 93.68 ± 6.48% total release until 96 h. In vitro, Octoprohibitin-CNPs showed lower cytotoxicity compared to Octoprohibitin alone. Time-kill kinetic and bacterial viability reduction assays showed Octoprohibitin-CNPs exhibited slightly higher antibacterial activity against A. baumannii than Octoprohibitin. Conclusions: Octoprohibitin-CNP-treated A. baumannii exhibited higher levels of morphological deviation, increased membrane permeability, and the production of reactive oxygen species, as well as antibiofilm activity with greater biofilm inhibition and eradication than Octoprohibitin. These findings show that Octoprohibitin-CNPs perform better against A. baumannii compared to Octoprohibitin alone. Full article

According to environmental concerns related to water pollution, this study aims to develop a novel hydrogel bead as a biocompatible and efficient adsorbent by integrating bacterial cellulose-activated carbon (BCAC) and montmorillonite (MT) in alginate hydrogel (ALG). The ionotropic gelation method was applied to the fabrication of BCAC/MT/ALG hydrogel beads. The BCAC/MT/ALG hydrogel bead exhibited significantly higher tensile strength, Young’s modulus, and thermal stability, with ~1.4 times higher adsorption uptake of methylene blue (MB) from aqueous solution as compared to the pristine ALG bead. The textural properties, including specific surface area and porosity, were beneficial to accommodate the size of cationic MB as the target molecule. This resulted in a remarkable MB adsorption uptake of 678.2 mg/g at pH 7 and 30 °C. The adsorption isotherm showed the best fit for the nonlinear Redlich-Peterson isotherm model. Experimental adsorption data were well-described by the pseudo-second order kinetic model, with R² values reaching 0.997. In addition, the adsorbent bead demonstrated easy regeneration with high reusability with approximately 75% of MB removal after being used for six cycles. Therefore, BCAC/MT/ALG bead represents an eco-friendly, cost-effective, and highly efficient adsorbent for MB removal from water and could potentially be used for removal of a wide range of cationic dye pollutants from wastewater. Full article

The aim of the study was to design microcapsules with a core of blueberry fruit extracts (Vaccinium myrtillus L.) using the ionotropic gelation method and then assess the effect of the type of extracts used and the combination of polymers on the profile of phenolic compounds, their in vitro bioavailability, stability during storage, as well as their antioxidant characteristics and cytotoxic activity against colon cancer cells while assessing biocompatibility against normal colon epithelial cells. Encapsulation efficiency (EE), ranging from 8.79 to 74.55%, significantly depended on the extract used and the type of carrier. It was shown that the addition of pectin (Pect) and whey protein isolate (WPI) to alginate (Alg) improved the efficiency of the encapsulation process. For this version of microcapsules, the highest antioxidant activity, phenolic compound content and their stability during storage were also demonstrated. The estimated content of phenolic compounds ranged from 0.48 to 40.07 mg/g, and the dominant compound was cyanidin 3-O-glucoside. In turn, the highest bioavailability of these compounds and the highest cytotoxic activity against cancer cells were characterized by microcapsules with Alg and WPI. Nevertheless, good biocompatibility with normal colon epithelial cells was demonstrated for all versions of microcapsules. The obtained data indicate that the tested variants of microcapsules protect the bioactive compounds of blueberry fruit extracts, which translates into maintaining their health-promoting properties. Full article