Search Results (64)

This study employs layer-by-layer self-assembly technology to develop novel antibacterial hemostatic microspheres to tackle significant blood loss and related complications resulting from accidents, surgeries, and natural disasters. By measuring the zeta potential and particle size of protamine, carboxymethyl starch (CMS), and hydroxypropyl trimethyl ammonium chloride chitosan (HACC), the optimal assembly conditions were determined. The optimal pH for the monolayer assembly is 3.0, with a CMS concentration of 3 mg/mL and a mass ratio of 1:4 between protamine and CMS, and the assembly process lasts for 2 h. The optimal assembly conditions for the bilayer assembly are a pH of 4.0, an HACC concentration of 1 mg/mL, and a mass ratio of the one-layer assembly to HACC of 1:2. The performance of the assembled microspheres was analyzed via antibacterial and coagulation experiments, revealing excellent antibacterial and coagulation effects, with inhibition rates against Escherichia coli and Bacillus subtilis both exceeding 99%, and a coagulation index of 0%. Additionally, the bilayer assembled microspheres also exhibited strong adsorption capacity and good biocompatibility. In summary, this study provides important scientific evidence for the development of new hemostatic materials, demonstrating significant clinical application potential. Full article

Background Despite many studies on polymer-incorporated nanocarriers for ophthalmic drug delivery, few have thoroughly explored the relationship between coating composition and performance. This study aimed to evaluate the effects of three commonly used cationic polymers—distearoyl phosphatidylethanolamine-polyethylene glycol 1000-poly(amidoamine) (DSPE-PEG1000-PAMAM), trimethyl chitosan (TMC), and (2,3-dioleoyloxypropyl) trimethylammonium chloride (DOTAP)—on the corneal behaviors and anti-cataract efficacy of diosmetin (DIO)-loaded micelles (D-M-P, D-M-T, and D-M-D, respectively). Methods The DIO-loaded micelles were prepared using the thin-film dispersion method and incorporated with the three polymers through hydrophobic interactions and electrostatic adsorption. Structural characterization was demonstrated by TEM imaging and particle size analyzer. In vitro release behavior was detected by the dialysis method. Cell viability of D-M-P, D-M-T, and D-M-D on L929 cells was detected by CCK-8 assays, with cellular uptake performed using coumarin 6 as the fluorescence indicator. Precorneal retention behaviors of these three vesicles were observed by In Vivo Imaging System. Transcorneal permeability was determined by modified Franz diffusion method and the permeation routes of the vesicles are investigated. Selenite-induced cataract model was established. The anti-cataract effects of three different DIO-loaded micelles were evaluated by the observation of lens opacity and antioxidant enzyme activities. Eye Irritation of the DIO in different preparations was estimated using the Draize test, along with H&E staining of the corneas. Results Structural characterization of DIO-loaded micelles revealed that the vesicles were spherical, with a uniform size distribution of around 28 nm, a similar surface potential of approximately 6.0 mV, and a high DIO entrapment efficiency of about 95%. Compared to the DIO suspension, all three formulations exhibited a significant sustained-release effect. They showed no signs of irritation and demonstrated increased IC50 values in L929 cells, indicating improved biocompatibility. Cellular uptake in human lens epithelial cells (HLECs) was assessed using confocal laser scanning microscopy. C-M-T displayed the highest fluorescence signals, with a cellular internalization 3.2 times greater than that of the solution group. Both C-M-T and C-M-P enhanced vesicle retention on the corneal surface by at least 47.8% compared to the Cou-6 solution. Furthermore, TMC facilitated the paracellular transport of vesicles into the deepest layers of the cornea and delivered DIO across the cornea, with a P_app value 3.11 times and 1.49 times those of D-M-D and D-M-P, respectively. In terms of therapeutic efficacy, D-M-T demonstrated the most significant attenuation of lens opacity, along with enhanced antioxidant enzyme activities and inhibition of lipid peroxidation. Conclusion The modification of micelle vesicles with different cationic polymers significantly influences their performance in ocular drug delivery. Among the tested formulations, D-M-T stands out due to its multiple advantages, including enhanced transcorneal drug delivery, therapeutic efficacy for DIO, and safety, making it the most promising candidate for ophthalmic applications. Full article

N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC), a quaternized chitosan derivative, has been shown to exhibit a broad spectrum of antimicrobial activity, especially against bacteria and enveloped viruses. Despite this, molecular docking studies showing its atomic-level mechanisms against these microorganisms are scarce. Here, for the first time, we employed molecular docking analyses to investigate the potential antibacterial activity of HTCC against Staphylococcus aureus and its antiviral activity against human immunodeficiency virus 1 (HIV-1). According to the findings, HTCC exhibited promising antibacterial activity with high binding affinities; however, it had limited antiviral activity. To validate these theoretical outcomes, experimental studies were conducted. Different derivatives of HTCC were synthesized and characterized using NMR, XRD, FTIR, and DLS. The in vitro assays validated the potent antibacterial efficacy of HTCC against S. aureus, whereas the antiviral studies did not show good antiviral activity. However, our research also revealed a promising avenue for further exploration of the antimicrobial activity of HTCC nanoparticles (NPs), since, thus far, no studies have been conducted to show the antiviral activity of HTCC NPs against HIV-1. The nanosized HTCC exhibited superior antiviral performance compared to the parent polymers, with complete (100%) inhibition of HIV-1 viral activity at the highest tested concentration (0.33 mg/mL). Full article

Multifunctional hydrogel dressings remain highly sought after for the promotion of skin wound regeneration. In the present study, multifunctional CHS-DA/HACC (CH) hydrogels with an interpenetrated network were constructed using hydroxypropyl trimethyl ammonium chloride modified chitosan (HACC) and dopamine-modified chondroitin sulfate (CHS-DA), using genipin as crosslinker. The synthesis of HACC and CHS-DA was effectively confirmed using Fourier transform infrared (FT-IR) analysis and ¹H nuclear magnetic resonance (¹H NMR) spectroscopy. The prepared CH hydrogels exhibited a network of interconnected pores within the microstructure. Furthermore, rheological testing demonstrated that CH hydrogels exhibited strong mechanical properties, stability, and injectability. Further characterization investigations showed that the CH hydrogels showed favorable self-healing and self-adhesion properties. It was also shown that increasing HACC concentration ratio was positively correlated with the antibacterial activity of CH hydrogels, as evidenced by their resistance to Escherichia coli and Staphylococcus aureus. Additionally, Cell Counting Kit-8 (CCK-8) tests, fluorescent images, and a cell scratch assay demonstrated that CH hydrogels had good biocompatibility and cell migration ability. The multifunctional interpenetrated network hydrogels were shown to have good antibacterial properties, antioxidant properties, stable storage modulus and loss modulus, injectable properties, self-healing properties, and biocompatibility, highlighting their potential as wound dressings in wound healing applications. Full article

The aim of the current study is to develop chitosan-based biomaterials which can sustainably release acetylsalicylic acid while presenting significant biological activity. Herein, an innovative ionic bonding strategy between hydroxypropyl trimethyl ammonium chloride chitosan (HACC) and acetylsalicylic acid (AA) was proposed, skillfully utilizing the electrostatic attraction of the ionic bond to achieve the controlled release of drugs. Based on this point, six crosslinked N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan acetylsalicylic acid salt (CHACAA) hydrogel films with varying acetylsalicylic acid contents were prepared by a crosslinking reaction. The results of ¹H nuclear magnetic resonance spectroscopy (¹H NMR) and scanning electron morphology (SEM) confirmed the crosslinked structure, while the obtained hydrogel films possessed favorable thermal stability, mechanical properties, and swelling ability. In addition, the drug release behavior of the hydrogel films was also investigated. As expected, the prepared hydrogel films demonstrated the capability for the sustainable release of acetylsalicylic acid due to ion pair attraction dynamics. Furthermore, the bioactivities of CHACAA-3 and CHACAA-4 hydrogel films with acetylsalicylic acid molar equivalents of 1.25 and 1.5 times those of HACC were particularly pronounced, which not only exhibited an excellent drug sustained-release ability and antibacterial effect, but also had a higher potential for binding and scavenging inflammatory factors, including NO and TNF-α. These findings suggest that CHACAA-3 and CHACAA-4 hydrogel films hold great potential for applications in wound dressing, tissue engineering scaffolds, and drug carriers. Full article

Dental caries (DC) is one of the most common oral diseases and is mainly caused by Streptococcus mutans (S. mutans). The use of antibiotics against S. mutans usually has side effects, including developing resistance. N-2-Hydroxypropyl trimethyl ammonium chloride chitosan (N-2-HACC), a natural product, has great potential utility in antibacterial agents owing to its low toxicity and good biocompatibility. Thus, the purpose of the present study was to explore the antimicrobial activity of N-2-HACC against S. mutans through the permeability of the cell wall, integrity of cell membrane, protein and nucleic acid synthesis, respiratory metabolism, and biofilm formation. Our results confirmed that the MIC of N-2-HACC against S. mutans was 0.625 mg/mL with a 90.01 ± 1.54% inhibition rate. SEM observed the formation of cavities on the surface of S. mutans after 12 h N-2-HACC treatment. The level of alkaline phosphatase (AKP) activity was higher in the N-2-HACC treatment group than in the control group, indicating that N-2-HACC can improve the permeability of the cell wall. Also, N-2-HACC treatment can destroy the cell membrane of S. mutans by increasing conductivity and absorbance at 260 nm, decreasing cell metabolic activity, and enhancing the fluorescence at 488 nm. Respiratory metabolism revealed that the activities of the Na⁺-K⁺-ATP enzyme, pyruvate kinase (PK), succinate dehydrogenase (SDH), and malate dehydrogenase (MDH) were decreased after N-2-HACC treatment, revealing that N-2-HACC can inhibit glycolysis and the tricarboxylic acid cycle (TCA cycle) of S. mutans. Moreover, N-2-HACC can also decrease the contents of the nucleic acid and solution protein of S. mutans, interfere with biofilm formation, and decrease the mRNA expression level of biofilm formation-related genes. Therefore, these results verify that N-2-HACC has strong antibacterial activity against S. mutans, acting via cell membrane integrity damage, increasing the permeability of cell walls, interfering with bacterial protein and nucleic acid synthesis, perturbing glycolysis and the TCA cycle, and inhibiting biofilm formation. It is suggested that N-2-HACC may represent a new potential synthetically modified antibacterial material against S. mutans. Full article

Safety and effectiveness are the cornerstone objectives of nanomedicine in developing nanotherapies. It is crucial to understand the biological interactions between nanoparticles and immune cells. This study focuses on the manufacture by the microfluidic technique of N-trimethyl chitosan/protein nanocarriers and their interaction with J774 cells to elucidate the cellular processes involved in absorption and their impact on the immune system, mainly through endocytosis, activation of lysosomes and intracellular degradation. TEM of the manufactured nanoparticles showed spherical morphology with an average diameter ranging from 36 ± 16 nm to 179 ± 92 nm, depending on the concentration of the cargo protein (0, 12, 55 μg/mL). FTIR showed the crosslinking between N-trimethyl chitosan and the sodium tripolyphosphate and the α-helix binding loss of BSA. TGA revealed an increase in the thermal stability of N-trimethyl chitosan/protein nanoparticles compared with the powder. The encapsulation of the cargo protein used was demonstrated using XPS. Their potential to improve cell permeability and use as nanocarriers in future vaccine formulations was demonstrated. The toxicity of the nanoparticles in HaCaT and J774 cells was studied, as well as the importance of evaluating the differentiation status of J774 cells. Thus, possible endocytosis pathways and their impact on the immune response were discussed. This allowed us to conclude that N-trimethyl chitosan nanoparticles show potential as carriers for the immune system. Still, more studies are required to understand their effectiveness and possible use in therapies. Full article

The chemical stability and ion transport properties of quaternized chitosan (QCS)-based anion exchange membranes (AEMs) were explored using Density Functional Theory (DFT) calculations and all-atom molecular dynamics (MD) simulations. DFT calculations of LUMO energies, reaction energies, and activation energies revealed an increasing stability trend among the head groups: propyl trimethyl ammonium chitosan (C) < oxy propyl trimethyl ammonium chitosan (B) < 2-hydroxy propyl trimethyl ammonium chitosan (A) at hydration levels (HLs) of 0 and 3. Subsequently, all-atom MD simulations evaluated the diffusion of hydroxide ions (${\mathrm{OH}}^{-}$) through mean square displacement (MSD) versus time curves. The diffusion coefficients of ${\mathrm{OH}}^{-}$ ions for the three types of QCS (A, B, and C) were observed to increase monotonically with HLs ranging from 3 to 15 and temperatures from 298 K to 350 K. Across different HLs and temperatures, the three QCS variants exhibited comparable diffusion coefficients, underlining their effectiveness in vehicular transport of ${\mathrm{OH}}^{-}$ ions. Full article

The focus of the present study is on the fabrication of effective and eco-friendly hybrid electrospun materials based on poly(L-lactide-co-D,L-lactide) (PLDLLA), Fe₃O₄ and ZnO with an appropriate design for antioxidant and photocatalytic performance. The design of the fibrous materials was purposely tailored in one step by electrospinning and simultaneous electrospinning/electrospraying. Electrospinning of PLDLLA and its mixture with Fe₃O₄ resulted in the fabrication of materials with design type “in”. Furthermore, the surface of the electrospun PLDLLA and Fe₃O₄-in-PLDLLA was decorated with ZnO particles by simultaneous electrospraying, thus materials with design type “on” were obtained. In this case, quaternized N,N,N-trimethyl chitosan iodide (QCOS) was used as a sticking agent of ZnO particles onto the fiber’s surface. Different structures and morphologies of the electrospun materials were observed by SEM equipped with EDX and TEM. TGA and XRD analyses show that the presence of inorganic particles had an impact on the thermal properties and crystallinity of the electrospun materials. Furthermore, the material type “on” showed improved wettability with a water contact angle less than 90° compared to the material type “in” with an angle larger than 90°. In particular, the presence of Fe₃O₄ imparts complementary magnetic properties, while ZnO considerably increased the antioxidant activity of the fibrous materials. Materials with design type “on” displayed over 70% radical scavenging capacity in contrast to the material type “in” with less than 20% capacity within 30 min of contact. Moreover, the purposely tailored design type “on” materials provided excellent photocatalytic degradation of model organic pollutant methylene blue dye under UV light irradiation even after 5-fold use, and at the end of the fifth cycle these materials degraded more than 90% of the dye. These results reveal not only a strategy for the fabrication of electrospun hybrid bio-based materials with targeted design but also provide a promising, simple and effective way for mitigating water pollution. Full article

In order to remove high-concentration emulsified oil from wastewater, a chitosan-based magnetic flocculant, denoted as FS@CTS-P(AM-DMC), was employed in this present study. The effects of factors including the magnetic flocculant dose, pH values, and coexisting ions were investigated. A comparative dosing mode with the assistance of polyacrylamide (PAM) was also included. The evolution of floc size was studied using microscopic observation to investigate the properties of flocs under different pH values and dosing modes. Particle image velocimetry (PIV) and extended Deryaguin–Landau–Verwey–Overbeek models were utilized to illustrate the distribution and velocity magnitude of the particle flow fields and to delve into the mechanism of magnetic flocculation. The results showed that FS@CTS-P(AM-DMC) achieved values of 96.4 and 74.5% for both turbidity and COD removal for 3000 mg/L of simulated emulsified oil. In the presence of PAM, the turbidity and COD removal reached 95.7 and 71.6%. In addition, FS@CTS-P(AM-DMC) demonstrated remarkable recycling and reusability performances, maintaining effective removal after eight cycles. The strength and recovery factors of magnetic flocs without PAM reached 69.3 and 76.8%, respectively. However, with the addition of PAM, they decreased to 46.73 and 51.47%, respectively. During the magnetophoretic processes, FS@CTS-P(AM-DMC) and oil droplets continuously collided and aggregated, forming three-dimensional network aggregates. Moreover, the magnetic floc generated a swirling motion, and the residual emulsified oil droplets could be further captured. Emulsified oil droplets were primarily removed through charge neutralization under acidic conditions. Under neutral and alkaline conditions, magnetic interactions played a major role in magnetic flocculation. Full article

The COVID-19 outbreak was a global pandemic with wide-ranging healthcare implications. Although several mRNA-based vaccines delivered using lipid nanoparticles (LNP) have been approved and demonstrated efficacy at reducing the severity and spread of infection, continued rapid viral evolution and disadvantages currently associated with LNP delivery vehicles (such as toxicity) are driving the design of next-generation SARS-CoV-2 vaccines. Herein, we describe the development of a trimethylated chitosan-based nanoparticle layer-by-layer (LbL) delivery platform for multiple antigens as a scalable and safe COVID-19 vaccine, known as, “LbL-CoV19”. These vaccine candidates have been demonstrated to be biocompatible, safe, and effective at stimulating both humoral and cellular responses for protection in preclinical studies. Preliminary results also indicate that LbL-CoV19 can potentially achieve rapid, long-lasting, and broad protection against the SARS-CoV-2 challenge. The “plug-and-play” platform technology is well suited to preparedness for future pandemics and disease outbreaks. Full article

Pears are abundant in bioactive compounds, which exert favorable effects on human health. The biophysical attributes of fruit cuticles are pivotal in determining fruit quality, storability, and susceptibility to mold growth. This study aimed to elucidate the biophysical properties of six pear cultivars, ‘Conference’, ‘Celina’, ‘Abate Fetel’, ‘Packham’s Triumph’, ‘Sweet Sensation’, and ‘Williams’. Two maturity stages, unripe and fully ripened, were investigated. Furthermore, the efficacy of trimethyl-chitosan-coated pear surfaces in preventing Penicillium expansum (P. expansum) growth was assessed. Basic maturity indices (CIE color, ethylene evolution, firmness, soluble solids), cuticle contact angle, roughness, and zeta potential were analyzed. Surface roughness was measured using an optical profilometer, hydrophobicity was measured via profilometry, and zeta potential was quantified using an electrokinetic analyzer. The ‘Celina’ cultivar exhibited the highest roughness, whereas ‘Williams’ had the lowest roughness. All the cultivars’ cuticles demonstrated hydrophilic characteristics, with contact angles ranging between 65° and 90°. For pH values exceeding 3.5, all pear surfaces exhibited a negative zeta potential. P. expansum growth was the slowest on the ‘Packham’s Triumph’ and ‘Conference’ cultivars. Treatment with trimethyl chitosan effectively inhibited P. expansum growth in the initial hours of incubation. In conclusion, diverse pear cultivars manifest distinct biophysical surface properties and varying susceptibility to P. expansum growth. The growth of P. expansum correlates positively with roughness, contact angle, and zeta potential. These differences can significantly impact shelf life potential and the overall postharvest quality of pears. Full article

Efficient drug delivery remains a critical challenge for treating neurodegenerative diseases, such as Alzheimer’s disease (AD). Using innovative nanomaterials, delivering current medications like acetylcholinesterase inhibitors to the brain through the intranasal route is a promising strategy for managing AD. Here, we developed a unique combinational drug delivery system based on N,N,N-trimethyl chitosan nanoparticles (NPs). These NPs encapsulate rivastigmine, the most potent acetylcholinesterase inhibitor, along with insulin, a complementary therapeutic agent. The spherical NPs exhibited a zeta potential of 17.6 mV, a size of 187.00 nm, and a polydispersity index (PDI) of 0.29. Our findings demonstrate significantly improved drug transport efficiency through sheep nasal mucosa using the NPs compared to drug solutions. The NPs exhibited transport efficiencies of 73.3% for rivastigmine and 96.9% for insulin, surpassing the efficiencies of the drug solutions, which showed transport efficiencies of 52% for rivastigmine and 21% for insulin ex vivo. These results highlight the potential of a new drug delivery system as a promising approach for enhancing nasal transport efficiency. These combinational mucoadhesive NPs offer a novel strategy for the simultaneous cerebral delivery of rivastigmine and insulin, which could prove helpful in developing effective treatments of AD and other neurodegenerative conditions. Full article

Wound management practices have made significant advancements, yet the search for improved antiseptics persists. In our pursuit of solutions that not only prevent infections but also address broader aspects of wound care, we investigated the impact of integrating trimethyl chitosan (TMC) into a widely used poly(vinylpyrrolidone)-iodine gel (PVP-I gel). Our study assessed the antimicrobial efficacy of the PVP gel with TMC against Escherichia coli, Staphylococcus aureus, multidrug-resistant S. aureus MRSA, and Candida albicans. Additionally, we compared hemostatic effects using a liver puncture bleeding model and evaluated wound healing through histological sections from full-thickness dermal wounds in rats. The results indicate that incorporating TMC into the commercially available PVP-I gel did not compromise its antimicrobial activity. The incorporation of TMC into the PVP-I gel markedly improves its hemostatic activity. The regular application of the PVP-I gel with TMC resulted in an increased blood vessel count in the wound bed and facilitated the development of thicker fibrous tissue with a regenerated epidermal layer. These findings suggest that TMC contributes not only to antimicrobial activity but also to the intricate processes of tissue regeneration. In conclusion, incorporating TMC proves beneficial, making it a valuable additive to commercially available antiseptic agents. Full article

The present study focused on the design and preparation of acid-responsive benzimidazole-chitosan quaternary ammonium salt (BIMIXHAC) nanogels for a controlled, slow-release of Doxorubicin HCl (DOX.HCl). The BIMIXHAC was crosslinked with sodium tripolyphosphate (TPP) using the ion crosslinking method. The method resulted in nanogels with low polydispersity index, small particle size, and positive zeta potential values, indicating the good stability of the nanogels. Compared to hydroxypropyl trimethyl ammonium chloride chitosan-Doxorubicin HCl-sodium tripolyphosphate (HACC-D-TPP) nanogel, the benzimidazole-chitosan quaternary ammonium salt-Doxorubicin HCl-sodium tripolyphosphate (BIMIXHAC-D-TPP) nanogel show higher drug encapsulation efficiency and loading capacity (BIMIXHAC-D-TPP 93.17 ± 0.27% and 31.17 ± 0.09%), with acid-responsive release profiles and accelerated release in vitro. The hydroxypropyl trimethyl ammonium chloride chitosan-sodium tripolyphosphate (HACC-TPP), and benzimidazole-chitosan quaternary ammonium salt-sodium tripolyphosphate (BIMIXHAC-TPP) nanogels demonstrated favorable antioxidant capability. The assay of cell viability, measured by the MTT assay, revealed that nanogels led to a significant reduction in the cell viability of two cancer cells: the human lung adenocarcinoma epithelial cell line (A549) and the human breast cancer cell line (MCF-7). Furthermore, the BIMIXHAC-D-TPP nanogel was 2.96 times less toxic than DOX.HCl to the mouse fibroblast cell line (L929). It was indicated that the BIMIXHAC-based nanogel with enhanced antioxidant and antitumor activities and acidic-responsive release could serve as a potential nanocarrier. Full article