N-trimethyl Chitosan Research Articles (Page 1)

Design, synthesis, and bioactivity evaluation of PABA-based five- and six-membered heterocyclic Schiff base quaternary ammonium chitosan derivatives.

Investigation of the bioactivities of N, N, N-trimethyl chitosan derivatives constructed with sulfonic zwitterionic moieties.

The present study developed a novel nano-structured nasal Bordetella pertussis vaccine candidate using encapsulating filamentous haemagglutinin (FHA) and pertussis toxoid (PTd) into N-trimethyl chitosan (TMC) with the help of CpG as an adjuvant and crosslinker (CpG-adjuvanted TMC/PTd-FHA), followed by physicochemical characterization and immune response evaluation after nasal administration. The TMC/CpG/PTd-FHA nanoparticle (NP) exhibited a particle size and zeta potential of 289.4 nm and +25.7 mV, respectively. The antigen/toxoid-loaded NPs exhibited >80% efficacy for encapsulation into polymer matrices, whereas in vitro antigen/toxoid release was found to be 95.18% after 96 hours. High immunization rates were observed in NP-treated mice with increased IgG and secretory IgA levels and proper capability to induce IFN-γ, IL-4, and IL-17 compared with the control group. Overall, nasal administration of the proposed approach, utilizing CpG as an adjuvant and crosslinker, could elicit humoral and Th1-type cellular immune responses, demonstrating promising potential as a vaccine delivery system.

Androgenetic alopecia (AGA) is currently the most prevalent cause of hair loss on the scalp. The daily administration of finasteride (FINA) by oral route may lead to the development of numerous undesirable systemic side effects. However, commercially available dermal dosage forms are available only with minoxidil; few studies have claimed severe side effects. Our study deals with the development of solid lipid nanoparticles (SLNs) of FINA with a suitable combination of l-α-phosphatidylcholine (LPC) and N-trimethyl chitosan (NTC) to overcome limitations along with good skin retention and hair growth. FINA-SLNs were developed using the ultrasonication technique and characterized further, along with hair growth observed in the animal model. The formulation NP7 showed the highest zeta potential value of -16.5 mV. The absence of the [double bond, length as m-dash]NH peak in the 1H-NMR spectra could be due to the protons attached, which have substantial exchangeability and result in a probable disappearance in the NMR spectra. The investigation showed the highest skin retention of 226.76 μg of FINA by NP7, along with a modest amount of FINA permeated (71.23 μg) during the study period of 18 h. The animal model using C57BL/6 mice showed a notable enhancement in hair covering and growth in Group IV, which received treatment without any visible cutaneous reaction on the skin. This outcome underscores the effectiveness and importance of the formulation developed using a suitable combination of LPC and NTC, which could be used to manage AGA effectively.

Upconversion nanoparticles (UCNPs), capable of converting near-infrared (NIR) light into high-energy emission, hold significant promise for bioimaging applications. However, the presence of tissue barriers poses a challenge to the effective delivery of nanoparticles (NPs) to target organs. In this study, we demonstrate the core–shell UCNPs modified with cationic biopolymer, i.e., N, N-trimethyl chitosan (TMC), can overcome endothelial barriers. The core–shell UCNP is composed of NaGdF4: Yb3+,Tm3+ (16.7 ± 2.7 nm) as core materials and silica (SiO2) shell. The average particle size of UCNPs@SiO2 is estimated at 26.1 ± 3.7 nm. X-ray diffraction (XRD), transmission electron microscopy (TEM) and element mapping shows the formation of hexagonal crystal structure of β-NaGdF4 and elements doping. The surface of UCNPs@SiO2 has been modified with poly(ethylene glycol) (PEG) to enhance water dispersibility and colloidal stability, and further modified with TMC with the zeta potential increasing from -2.1 ± 0.96 mV to 26.9 ± 12.6 mV. No significant toxic effect is imposed to HUVECs when the cells are treated with core–shell UCNPs with surface modification up to 250 µg/mL. The transport ability of the core–shell UCNPs has been evaluated by using the in vitro endothelial barrier model. Transepithelial electrical resistance (TEER) and immunofluorescence staining of tight junction proteins have been employed to verify the integrity of the in vitro endothelial barrier model. The results indicate that the transport percentage of the UCNPs@SiO2 with PEG and TMC through the model is up to 4.56%, which is twice higher than that of the UCNPs@SiO2 with PEG but without TMC and six times that of the UCNPs@SiO2.

The development of multifunctional cotton fabrics that are stain-resistant, antimicrobial, and easy to clean has sparked scientific interest as well as practical usefulness, owing to its medical and healthcare applications. The purpose of this study was to fabricate self-cleaning and antimicrobial cotton for final use by soaking the cotton fabric in nonfluorinated hybrid formulations based on quaternary chitosan-silane using the sol-gel process. The fluorine-free cotton fabric demonstrated high self-cleaning behavior and outstanding bacterial killing efficacy against E. coli and S. aureus bacteria, without altering the desired textile properties of cotton fabric. Remarkably, cotton textiles using the hybrid formulations HTACC-VTES (N-(2-hydroxy)propyl-3-trimethylammonium chitosan chloride-vinyltriethoxy silane) and TMCC-VTES (N, N, N-trimethyl chitosan chloride-vinyltriethoxy silane) demonstrated promising water contact angles of 147° and 142° respectively, indicating a move toward superhydrophobicity. In FTIR spectra, both treated cotton textiles had an absorption peak at 1208 cm-1 (SiOC bending), indicating a stronger interaction between silane binding agents and the cotton substrate. The treated cotton fabric with desirable features retains its stability and endurance after 12 cycles of washing for antibacterial tests and 15 cycles for wettability tests. The manufactured cotton fabric has several potential applications, such as in personal hygiene items and medical applications.

Colonic targeting insulin-loaded trimethyl chitosan nanoparticles coated pectin for oral delivery: In vitro and In vivo studies

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.

N-trimethyl chitosan and tripalmitin loaded solid lipid nanoparticles of tofacitinib citrate: Characterization and in-vivo anti-inflammatory assessment

Induction of humoral and cell-mediated immunity in mice by chitosan-curdlan composite nanoparticles administered intranasally and subcutaneously

This work proposes a feasible, reproducible, and low-cost modified method to manufacture chitosan, chitosan/IgG-protein-loaded, and trimethylated chitosan nanoparticles, using microfluidics combined with the microemulsion technique, which differs from the traditional batch process of chitosan-based nanoparticles. The synthesis process consists of generating microreactors of chitosan-based polymer in a poly-dimethylsiloxane ψ-shaped microfluidic device and then crosslinking with sodium tripolyphosphate outside the cell. Transmission electron microscopy demonstrates an improvement in size control and distribution of the solid-shape chitosan nanoparticles (~80 nm) compared to the batch synthesis. Regarding chitosan/IgG-protein-loaded nanoparticles, these presented a core-shell morphology having a diameter of close to 15 nm. Raman and X-ray photoelectron spectroscopies confirmed the ionic crosslinking between the amino groups of chitosan and the phosphate groups of sodium tripolyphosphate in the fabricated samples and the total encapsulation of IgG protein during the fabrication of chitosan/IgG-loaded nanoparticles. Then, an ionic crosslinking and nucleation-diffusion process of chitosan-sodium tripolyphosphate was carried out during the nanoparticle formation, with and without IgG protein loading. The use of N-trimethyl chloride chitosan nanoparticles in vitro on human-keratinocyte-derived cell line HaCaT did not show side effects independently of its concentration from 1 to 10 μg/mL. Therefore, the proposed materials could be used as potential carrier-delivery systems.

N-Trimethylated chitosan coating white adipose tissue vascular-targeting oral nano-system for the enhanced anti-obesity effects of celastrol

A bivalent form of nanoparticle-based dengue vaccine stimulated responses that potently eliminate both DENV-2 particles and DENV-2-infected cells.

Synthesis of biodegradable antimicrobial pH-sensitive silver nanocomposites reliant on chitosan and carrageenan derivatives for 5-fluorouracil drug delivery toward HCT116 cancer cells

Antimicrobial materials are considered potential alternatives to prevent the development of biofilm-associated contaminations. Concerns regarding synthetic preservatives necessitate the development of innovative and safe natural antimicrobials. In the present study, we discuss the in situ infrared attenuated total reflection spectroscopy (IR-ATR) investigations of the selective antimicrobial efficiency of chitosan in controlling the growth of Lentilactobacillus parabuchneri biofilms. The protonated charges of chitosan were additionally amplified by structural modification via methylation, yielding quaternized derivative TMC (i.e., N, N, N-trimethyl chitosan). To evaluate antimicrobial effectiveness against L. parab. biofilms, IR-ATR spectroscopy provided information on molecular mechanisms and insights into chemical changes during real-time biofilm inhibition studies. The integrated fiberoptic oxygen microsensors enabled monitoring oxygen (O2) concentration gradients within biofilms, thereby confirming the metabolic oxygen depletion dropping from 4.5 to 0.7 mg L−1. IR studies revealed strong electrostatic interactions between chitosan/its water-soluble derivative and bacteria, indicating that a few hours were sufficient to affect biofilm disruption. The significant decrease in the IR bands is related to the characteristic spectral information of amide I, II, III, nucleic acid, and extracellular polymeric matrix (EPS) produced by L. parabuchneri biofilms. Cell clusters of biofilms, microcolonies, and destabilization of the EPS matrix after the addition of biopolymers were visualized using optical microscopy. In addition, scanning electron microscopy (SEM) of biofilms grown on polystyrene and stainless-steel surfaces was used to examine morphological changes, indicating the disintegration of the biofilm matrix into individual cells. Quantification of the total biofilm formation correlated with the CV assay results, indicating cell death and lysis. The electrostatic interactions between chitosan and the bacterial cell wall typically occur between protonated amino groups and negatively charged phospholipids, which promote permeabilization. Biofilm growth inhibition was assessed by a viability assay for a period of 72 h and in the range of low MIC values (varying 0.01–2%). These results support the potential of chitosan and TMC for bacterial growth prevention of the foodborne contaminant L. parabuchneri in the dairy industry and for further implementation in food packaging.

The nasal passage is the primary entry point for many infectious agents. Therefore, nasal vaccines that can overcome the limitations associated with antigen uptake are likely to play an important role in protecting these infectious agents. Thus, adjuvants and antigen-carrying systems that can induce a suitable mucosal and systemic immune response against their accompanying antigens are highly important. In this study, synthetic oligodeoxynucleotides containing CpG motifs (CpG-ODN) accompanied by the recombinant ectodomain of influenza M2 protein were encapsulated in N-trimethyl chitosan (TMC) nanoparticles. After the preparation of TMC nanoparticles, the morphological characteristics and loading efficiency and in vitro antigen release, as well as their ability to induce efficient immune responses against M2e in intranasal inoculation in the mouse model, were studied. Based on the size and zeta potential of the nanoparticles prepared in this study, it was determined that they were all nanosized, and their positive zeta potential ranged from 25 to 28 mV, while their polydispersity index was between 0.1 to 0.2, indicating a narrow range of particle sizes. A significant increase in serum levels of the total M2e-specific IgG antibody and BALF anti-M2e IgA was observed in mice intranasally immunized with M2e/CpG-ODN/TMC as opposed to those that were intranasally immunized with M2e/TMC, M2e/CpG-ODN, free M2e, and CpG-ODN/TMC. There was also a significant change in the IgG2a/IgG1 ratio in favour of IgG2a seems that CpG-ODN is responsible for directing the immune system towards Th1. Our findings show that CpG-ODN can significantly enhance the mucosal and systemic humoral immune response against M2e when encapsulated in a suitable carrier such as TMC for intranasal administration. In conclusion, when combined with a suitable carrier, CpG-ODN can be considered an effective adjuvant for mucosal administration.

The microtubule-associated protein tau is involved in more than 20 different neurological disorders characterized by aberrant intracellular aggregation of tau in the brain. Here, we investigated the aggregation of a novel 20-residue model peptide, tau298-317, which is derived from the key microtubule binding domain of the full sequence tau. Our results show that tau298-317 highly mimics the physical and aggregation properties of tau. Under normal physiological conditions, the peptide maintains a disordered random coil without aggregation. The presence of polyanionic heparin (Hep) significantly promotes the aggregation of this peptide to form amyloid fibrils. The Hep-induced aggregation is sensitive to the ionic strength of the solution and the introduction of the negatively charged phosphate group on a serine (Ser305) residue in the sequence, suggesting an important role of electrostatic interactions in the mechanism of Hep-mediated aggregation. In addition, two positively charged polysaccharides, chitosan (CHT) and its quaternary derivative N-trimethyl chitosan (TMC), were found to effectively inhibit Hep-induced aggregation of tau298-317 in a concentration-dependent manner. Attractive electrostatic interactions between the positively charged moieties in CHT/TMC and the negatively charged residues of Hep play a critical role in inhibiting Hep-peptide interactions and suppressing peptide aggregation. Our results suggest that positively charged polyelectrolytes with optimized charged groups and charge distribution patterns can serve as effective molecular candidates to block tau-Hep interactions and prevent aggregation of tau induced by Hep and other polyanions.

Dengue is a disease that poses a significant global public health concern. Although a tetravalent live-attenuated dengue vaccine has been licensed, its efficacy is still debated due to evidence of vaccine breakthrough infection. To avoid this issue, dengue vaccines should stimulate a high degree of serotype-specific response. Thus, envelope domain III (EDIII), which contains serotype-specific neutralizing epitopes, is an attractive target for dengue vaccine development. In this study, we investigated how EDIII encapsidated in N, N, N-trimethyl chitosan chloride nanoparticles (TMC NPs) stimulates a serotype-specific response and whether this response exerts a potential in vitro breakthrough infection. The immune response to DENV-2 elicited by EDIII TMC NP-immunized mice was monitored. We demonstrated that immunization with EDIII TMC NPs resulted in a high level of anti-EDIII antibody production. These antibodies included IgG, IgG1, and IgG2a subtypes. Importantly, antibodies from the immunized mice exerted efficient neutralizing activity with undetectable antibody dependent enhancement (ADE) activity. We also found that EDIII TMC NPs activated functional EDIII-specific CD4+ and CD8+ T cell responses. In conclusion, EDIII TMC NPs stimulated humoral immunity with a strong neutralizing antibody response, as well as a cellular immune response against DENV-2.

N-trimethyl chitosan coated targeting nanoparticles improve the oral bioavailability and antioxidant activity of vitexin

Effects of N-trimethyl chitosan-recombinant tissue factor pathway inhibitor complex on avulsion flap with roll compaction in rat