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Abstract Background Oral ulcers are a common side effect of chemotherapy and affect patients’ quality of life. While stem cell transplantation is a potential treatment for oral ulcers, its efficacy is limited as the stem cells tend to remain in the affected area for a short time. This study aims to develop a treatment for oral ulcers by using trimethyl chitosan (TMC) hydrogel with human tonsil-derived stem cells (hTMSCs) to increase the therapeutic effect of stem cells and investigate their effectiveness. Methods Animals were divided into four experimental groups: Control, TMC hydrogel, hTMSCs, and hTMSCs loaded in TMC hydrogel (Hydrogel + hTMSCs) (each n = 8). Oral ulcers were chemically induced by anesthetizing the rats followed by injection of dilute acetic acid in the right buccal mucosa. After confirming the presence of oral ulcers in the animals, a single subcutaneous injection of 100 µL of each treatment was applied to the ulcer area. Histological analyses were performed to measure inflammatory cells, oral mucosal thickness, and fibrosis levels. The expression level of inflammatory cytokines was also measured using RT-PCR to gauge therapeutic the effect. Results The ulcer size was significantly reduced in the TMC hydrogel + hTMSCs group compared to the control group. The stem cells in the tissue were only observed until Day 3 in the hTMSCs treated group, while the injected stem cells in the TMC Hydrogel + hTMSCs group were still present until day 7. Cytokine analysis related to the inflammatory response in the tissue confirmed that the TMC Hydrogel + hTMSCs treated group demonstrated superior wound healing compared to other experimental groups. Conclusion This study has shown that the adhesion and viability of current stem cell therapies can be resolved by utilizing a hydrogel prepared with TMC and combining it with hTMSCs. The combined treatment can promote rapid healing of oral cavity wounds by enhancing anti-inflammatory effects and expediting wound healing. Therefore, hTMSC loaded in TMC hydrogel was the most effective wound-healing approach among all four treatment groups prolonging stem cell survival. However, further research is necessary to minimize the initial inflammatory response of biomaterials and assess the safety and long-term effects for potential clinical applications.

Background: Oral ulcers are a common side effect of chemotherapy and affect patients' quality of life. While stem cell transplantation is a potential treatment for oral ulcers, its efficacy is limited as the stem cells tend to remain in the affected area for a short time. This study aims to develop a treatment for oral ulcers by using trimethyl chitosan (TMC) hydrogel with human tonsil-derived stem cells (hTMSCs) to increase the therapeutic effect of stem cells and investigate their effectiveness. Methods: Animals were divided into four experimental groups: Control, TMC hydrogel, hTMSCs, and hTMSCs loaded in TMC hydrogel (Hydrogel + hTMSCs) (each n = 8). Oral ulcers were chemically induced by anesthetizing the rats followed by injection of dilute acetic acid in the right buccal mucosa. After confirming the presence of oral ulcers in the animals, a single subcutaneous injection of 100 µL of each treatment was applied to the ulcer area. Histological analyses were performed to measure inflammatory cells, oral mucosal thickness, and fibrosis levels. The expression level of inflammatory cytokines was also measured using RT-PCR to gauge therapeutic the effect. Results: The ulcer size was significantly reduced in the TMC hydrogel + hTMSCs group compared to the control group. The stem cells in the tissue were only observed until Day 3 in the hTMSCs treated group, while the injected stem cells in the TMC Hydrogel + hTMSCs group were still present until day 7. Cytokine analysis related to the inflammatory response in the tissue confirmed that the TMC Hydrogel + hTMSCs treated group demonstrated superior wound healing compared to other experimental groups. Conclusion: This study has shown that the adhesion and viability of current stem cell therapies can be resolved by utilizing a hydrogel prepared with TMC and combining it with hTMSCs. The combined treatment can promote rapid healing of oral cavity wounds by enhancing anti-inflammatory effects and expediting wound healing. Therefore, hTMSC loaded in TMC hydrogel was the most effective wound-healing approach among all four treatment groups prolonging stem cell survival. However, further research is necessary to minimize the initial inflammatory response of biomaterials and assess the safety and long-term effects for potential clinical applications. [ABSTRACT FROM AUTHOR]

Gold nanoparticles (AuNPs) are arguably the most promising in terms of application among the noble metal nanoparticles. As such, researchers have dedicated a considerable amount of energy towards the synthesis of novel gold nanoparticles with different morphology and size, which in turn affect its potential application. This study synthesized novel spherical-shaped AuNPs via green reduction of gold ion in an aqueous solution of HAuCl4.3H2O in the presence of trimethyl chitosan as a stabilizing agent and pressurized H2 gas as a reducing agent on an ice water. The size, morphology, chemical composition, chemical environment and optical activities were examined by scanning electron microscope (SEM), high-resolution transmission electron microscope (HRTEM), x-ray photoelectron spectroscopy (XPS), and ultraviolet–visible spectroscopy (Uv–Visible), respectively. The average particle size of AuNPs is 37 nm while HR-TEM revealed a unique spherical morphology. The Tauc’s plot calculation revealed a band gap of 5.0 eV. This unique morphology and optical local field enhancement in plasmonic nanocomposites could be suitable alternative for conducting devices and photocatalysis. [ABSTRACT FROM AUTHOR]

Diosmin is a flavonoid derived from plants, possessing anti-inflammatory, antioxidant, antidiabetic, neuroprotective and cardiovascular protective properties. However, diosmin has low solubility in water, leading to low bioavailability. In this study, we constructed bilayer nanoparticles with trimethyl chitosan and soy peptides to improve the oral bioaccessibility and bioavailability of diosmin, and determined the characteristics and antioxidant properties of the diosmin-loaded nanoparticles. The results showed that the size of the nanoparticles was around 250 nm with the encapsulation efficiency higher than 97 %, and the nanoparticles were stable under regular conditions. In vitro digestion suggested the nanoparticles could protect diosmin from releasing in gastric digestion but promote the bioaccessibility of diosmin in intestine. Furthermore, the diosmin-loaded nanoparticles presented excellent antioxidant activities in vitro and significantly decreased the Lipopolysaccharides-induced brain Malondialdehyde (MDA) level by oral administration. Therefore, the reported nanoparticles may be an effective platform for improving the oral bioavailability of diosmin.

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. [ABSTRACT FROM AUTHOR]

Fine dust and bioaerosols are significant public health concerns, showing the importance of protective measures. In this study, natural-based trimethyl chitosan, permanently burdened with a positive charge, was successfully distributed on the surface of melt-blown polypropylene sheets through a metal rod coating process. This surface modification was confirmed through scanning electron microscopy and X-ray photoelectron spectroscopy, indicating the surface adsorption of trimethyl chitosan without chemical bonding. Modifying polypropylene mask filters yielded a positive surface zeta potential for 10–20 g/m2 coat weight, increasing the filtration efficiency to 55–94 % in a standard particle filtration test using paraffin oil as a liquid aerosol. The filtration efficiency remained higher than conventional non-treated mask filters even after the humidification of sheets. In addition, the filtration test against fine dust particles, such as titanium dioxide, was performed with trimethyl chitosan-modified mask filters that captured up to 100–800 µg/m3 titanium oxide particle concentrations, showing better filtration than conventional mask filters in high fine dust events. Trimethyl chitosan-modified mask filters also exhibited potent inhibition, bactericidal, and antiviral effects against HCoV-OC43, reducing the virus infection rate by 93.69 %. Thus, trimethyl chitosan could be applied to several existing filter membranes to protect against particulate matter and dangerous airborne pathogens.

In this study, we tested the biosorption capacity of trimethyl chitosan (TMC)-ZnO nanocomposite (NC) for the adsorptive removal of Escherichia coli (E. coli) in aqueous suspension. For the formation of ZnO NPs, we followed the green synthesis route involving Terminalia mantaly (TM) aqueous leaf extract as a reducing agent, and the formed ZnO particles were surface-coated with TMC biopolymer. On testing of the physicochemical characteristics, the TM@ZnO/TMC (NC) hydrogel showed a random spherical morphology with an average size of 31.8 ± 2.6 nm and a crystal size of 28.0 ± 7.7 nm. The zeta potential of the composite was measured to be 23.5 mV with a BET surface area of 3.01 m2 g−1. The spectral profiles of TM@ZnO/TMC NC hydrogel on interaction with Escherichia coli (E. coli) revealed some conformational changes to the functional groups assigned to the stretching vibrations of N-H, C-O-C, C-O ring, and C=O bonds. The adsorption kinetics of TM@ZnO/TMC NC hydrogel revealed the pseudo-second-order as the best fit mechanism for the E. coli biosorption. The surface homogeneity and monolayer adsorption of the TM@ZnO/TMC NC hydrogel reflects majorly the entire adsorption mechanism, observed to display the highest correlation for Jovanovic, Redlich–Peterson, and Langmuir's isotherm models. Further, with the use of TM@ZnO/TMC NC hydrogel, we measured the highest adsorption capacity of E. coli to be 4.90 × 10 mg g−1, where an in-depth mechanistic pathway was proposed by making use of the FTIR analysis. [ABSTRACT FROM AUTHOR]

Amphotericin B (AmB) is an effective antifungal agent; however, the application of AmB is associated with a number of drawbacks. Application of nanoparticles (NPs) is known to improve the efficiency of drug delivery to the target tissues, compared to the traditional methods. In this study, a novel method of NPs preparation was developed. The trimethyl chitosan (TMC) was synthesized using low molecular weight chitosan and was used for the preparation of TMC-NPs through ionic gelation method. Afterward, AmB-loaded TMC-NPs (TMC-NPs/AmB) were prepared and their drug delivery potential was testes. The TMC-NPs and TMC-NPs/AmB were characterized for their structure, particle size, Zeta potential, polydispersity index, morphology, loading efficiency, loading capacity, in vitro release profile, release kinetic, and entrapped AmB potency. The cytotoxicity and antifungal activity of TMC-NPs/AmB against Candida albicans biofilm were evaluated. The quaternization of TMC was estimated to be 36.4%. The mean particle size of TMC-NPs and TMC NPs/AmB were 210±15 and 365±10 nm, respectively, with a PDI of 0.30 and 0.4, ZP of +34±0.5 and +28±0.5 mV, respectively. Electron microscopy analysis indicated uniform spherical shapes with smooth surfaces. The TMC-NPs/AmB indicated LE of 76% and LC of 74.04 % with a potency of 110%. The release profile of TMC-NPs/AmB was best explained by the Higuchi model. The initial release after 10 h was obtained at 38%, and the rates of release after 36 and 84 h were determined at 67% and 76% respectively, which was significantly different (P

In this study, we tested the biosorption capacity of trimethyl chitosan (TMC)-ZnO nanocomposite (NC) for the adsorptive removal of Escherichia coli (E. coli) in aqueous suspension. For the formation of ZnO NPs, we followed the green synthesis route involving Terminalia mantaly (TM) aqueous leaf extract as a reducing agent, and the formed ZnO particles were surface-coated with TMC biopolymer. On testing of the physicochemical characteristics, the TM@ZnO/TMC (NC) hydrogel showed a random spherical morphology with an average size of 31.8 ± 2.6 nm and a crystal size of 28.0 ± 7.7 nm. The zeta potential of the composite was measured to be 23.5 mV with a BET surface area of 3.01 m2 g−1. The spectral profiles of TM@ZnO/TMC NC hydrogel on interaction with Escherichia coli (E. coli) revealed some conformational changes to the functional groups assigned to the stretching vibrations of N-H, C-O-C, C-O ring, and C=O bonds. The adsorption kinetics of TM@ZnO/TMC NC hydrogel revealed the pseudo-second-order as the best fit mechanism for the E. coli biosorption. The surface homogeneity and monolayer adsorption of the TM@ZnO/TMC NC hydrogel reflects majorly the entire adsorption mechanism, observed to display the highest correlation for Jovanovic, Redlich–Peterson, and Langmuir’s isotherm models. Further, with the use of TM@ZnO/TMC NC hydrogel, we measured the highest adsorption capacity of E. coli to be 4.90 × 10 mg g−1, where an in-depth mechanistic pathway was proposed by making use of the FTIR analysis.

Oral delivery of therapeutic peptides has been a daunting challenge due to poor transport across the tight junctions and susceptibility to enzymatic degradation in the gastrointestinal tract. Numerous advancement in nanomedicine has been made for the effective delivery of protein and peptide. Owing to the superior performance of chitosan in opening intercellular tight junctions of epithelium and excellent mucoadhesive properties, chitosan-based nanocarriers have recently garnered considerable attention, which was formulated in this paper to orally deliver the GLP-1 drug (Exenatide). Against this backdrop, we used chitosan (CS) polymers to encapsulate the exenatide, sodium tripolyphosphate (TPP) as the cross-linking agent and coated the exterior with sodium alginate (ALG) to impart the stability in an acidic environment. The chitosan/alginate nanoparticles (CS-TPP-ALG) functioned as a protective exenatide carrier, realized efficient cellular uptake and controlled release, leading to a steady hypoglycemic effect and a good oral bioavailability in vivo. Trimethyl chitosan (TMC), a chitosan derivative with stronger positive electrical properties was additionally selected as a substitute for chitosan to construct the TMC-TPP-ALG nanoparticle, and its oral peptide delivery capacity was explored in terms of both characterization and pharmacodynamics studies. Overall, our study demonstrated that functional chitosan/alginate nanoparticles can protect proteins from enzymatic degradation and enhance oral absorption, which presents important research value and application prospects. [ABSTRACT FROM AUTHOR]

This research aimed to study SiO2/quaternary-chitosan-coated magnetic material synthesis using the sol-gel method through two synthetic routes. The step of Route 1 was the methylation of the amine group on chitosan using methyl iodide and sodium hydroxide with dimethylformamide: water (1:1) as a solvent at room temperature for 48 hours to produce trimethyl chitosan. The next step was the sol-gel reaction. The magnetic was coated with silica and then added to the trimethyl chitosan solution that has reacted with (3-glycidyloxypropyl)trimethoxysilane as a crosslinker. Whereas Route 2 was the opposite of route 1, magnetic coating with chitosan silica was carried out first through the sol-gel reaction, followed by the methylation reaction. The synthesis results were characterized by their functional group, structure, crystal size, magnetic properties, and morphology. The Fe3O4/SiO2/quaternary-chitosan material was successfully synthesized, as indicated by the increase in the specific absorption band for C-H methyl and the decrease in the N-H amine absorption. Route 1 produced material with more quaternary ammonium groups and porous surface but inhomogeneous, while Route 2 produced thicker magnetic coatings. Both materials had stability in the range of pH 3-6 so that they could be applied as adsorbents for anionic compounds in this range. [ABSTRACT FROM AUTHOR]

Maliheh Hajiramezanali,1 Fatemeh Atyabi,2,3 Mona Mosayebnia,1 Mehdi Akhlaghi,4 Parham Geramifar,4 Amir Reza Jalilian,4 Seyed Mohammad Mazidi,5 Hassan Yousefnia,6 Soraya Shahhosseini,7 Davood Beiki4 1Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 2Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 3Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 4Research Center for Nuclear Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; 5Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran; 6Material and Nuclear Fuel Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran; 7Department of Radiopharmacy and Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran Introduction: Nowadays, nanoparticles (NPs) have attracted much attention in biomedical imaging due to their unique magnetic and optical characteristics. Superparamagnetic iron oxide nanoparticles (SPIONs) are the prosperous group of NPs with the capability to apply as magnetic resonance imaging (MRI) contrast agents. Radiolabeling of targeted SPIONs with positron emitters can develop dual positron emission tomography (PET)/MRI agents to achieve better diagnosis of clinical conditions.Methods: In this work, N,N,N-trimethyl chitosan (TMC)-coated magnetic nanoparticles (MNPs) conjugated to S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (DOTA) as a radioisotope chelator and bombesin (BN) as a targeting peptide (DOTA–BN–TMC–MNPs) were prepared and validated using fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), and powder X-ray diffraction (PXRD) tests. Final NPs were radiolabeled with gallium-68 (68Ga) and evaluated in vitro and in vivo as a potential PET/MRI probe for breast cancer (BC) detection.Results: The DOTA–BN–TMC–MNPs with a particle size between 20 and 30 nm were efficiently labeled with 68Ga (radiochemical purity higher than 98% using thin layer chromatography (TLC)). The radiolabeled NPs showed insignificant toxicity (>74% cell viability) and high affinity (IC50=8.79 µg/mL) for the gastrin-releasing peptide (GRP)-avid BC T-47D cells using competitive binding assay against 99mTc–hydrazinonicotinamide (HYNIC)–gamma-aminobutyric acid (GABA)–BN (7–14). PET and MRI showed visible uptake of NPs by T-47D tumors in xenograft mouse models.Conclusion: 68Ga–DOTA–BN–TMC–MNPs could be a potential diagnostic probe to detect BC using PET/MRI technique. Keywords: superparamagnetic iron oxide nanoparticles, trimethyl chitosan, bombesin, gallium-68, PET/MRI

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Anshu Malik,* Manish Gupta,* Vatika Gupta, Himanshu Gogoi, Rakesh Bhatnagar Molecular Biology and Genetic Engineering Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India *These authors contributed equally to this work Abstract: The application of natural carbohydrate polysaccharides for antigen delivery and its adjuvanation potential has garnered interest in the scientific community in the recent years. These biomaterials are considered favorable candidates for adjuvant development due to their desirable properties like enormous bioavailability, non-toxicity, biodegradability, stability, affordability, and immunostimulating ability. Chitosan is the one such extensively studied natural polymer which has been appreciated for its excellent applications in pharmaceuticals. Trimethyl chitosan (TMC), a derivative of chitosan, possesses these properties. In addition it has the properties of high aqueous solubility, high charge density, mucoadhesive, permeation enhancing (ability to cross tight junction), and stability over a range of ionic conditions which makes the spectrum of its applicability much broader. It has also been seen to perform analogously to alum, complete Freund’s adjuvant, incomplete Freund’s adjuvant, and cyclic guanosine monophosphate adjuvanation, which justifies its role as a potent adjuvant. Although many review articles detailing the applications of chitosan in vaccine delivery are available, a comprehensive review of the applications of TMC as an adjuvant is not available to date. This article provides a comprehensive overview of structural and chemical properties of TMC which affect its adjuvant characteristics; the efficacy of various delivery routes for TMC antigen combination; and the recent advances in the elucidation of its mechanism of action. Keywords: trimethyl chitosan, chitosan, vaccine delivery, adjuvant, polymer

Morteza Abkar,1 Mahdi Fasihi-Ramandi,2 Hamid Kooshki,3 Abbas Sahebghadam Lotfi4 1Nanomedicine and Nanobiology Research Center, Shiraz University of Medical Sciences, Shiraz, 2Molecular Biology Research Center, 3Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, 4Department of Clinical Biochemistry, Faculty of Medicine, Tarbiat Modares University, Tehran, Iran Abstract: Brucellosis is a group of closely associated zoonotic bacterial illnesses caused by members of the genus Brucella. B. melitensis Omp31 is a promising candidate for a subunit vaccine against brucellosis. This study surveyed the immunogenicity of Omp31 alone and with incomplete Freund’s adjuvant (Omp31-IFA) and N-trimethyl chitosan (TMC/Omp31) nanoparticles (NPs), as well as the effect of Omp31 immunization route on immunological responses and protection. After expression and purification, the recombinant Omp31 (rOmp31) was loaded onto TMC NPs by ionic gelation. The particle size, loading efficiency and in vitro release of the NPs were examined. Omp31-IFA was administered intraperitoneally, while TMC/Omp31 NPs were administered orally and intraperitoneally. According to the antibody subclasses and cytokine profile, intraperitoneal immunization by Omp31-IFA and TMC/Omp31 NPs induced T helper 1 (Th1) and Th1–Th2 immune responses, respectively. On the other hand, oral immunization with TMC/Omp31 NPs elicited a mixed Th1–Th17 immune response. Data obtained from the cell proliferation assay showed that vaccination with Omp31 stimulated a vigorous antigen-specific cell proliferative response, which could be further increased after oral immunization with TMC/Omp31 NPs. Vaccinated groups of mice when challenged with B. melitensis 16M were found to be significantly protected in the orally administered group in comparison with the intraperitoneally immunized mice. Results of this study indicated that the reason for high protection after oral vaccination can be via elicited Th17 response. Keywords: brucellosis, Th17, trimethyl chitosan, vaccine, nanoparticle

For efficient mucosal vaccine delivery, nanoparticulate antigens are better taken by microfold cells in the nasal associated lymphoid tissue and also dendritic cells. Nanoparticles based on polymers such as chitosan (CHT) and its water soluble derivative, trimethylchitosan (TMC), could be successfully used as carrier/adjuvant for this purpose. Sodium alginate, a negatively charged biopolymer, could modify the immunostimulatory properties of CHT and TMC NPs and increase their stability. Sodium alginate (ALG)-coated chitosan (CHT) and trimethylchitosan (TMC) nanoparticles (NPs) loaded with inactivated PR8 influenza virus were successfully prepared by direct coating of the virus with CHT or TMC polymers to evaluate their immunoadjuvant potential after nasal immunization. After nasal immunizations in BALB/c mice, PR8-CHT formulation elicited higher IgG2a and IgG1 antibody titers compared with PR8-TMC. ALG coating of this formulation (PR8-CHT-ALG) significantly decreased the antibody titers and a less immune response was induced than PR8-TMC-ALG formulation. PR8-TMC-ALG formulation showed significantly higher IgG2a/IgG1 ratio, as criteria for Th1-type immune response, compared with PR8-CHT-ALG and PR8 virus alone. Altogether, the PR8-TMC-ALG formulation could be considered as an efficient intranasal antigen delivery system for nasal vaccines. [ABSTRACT FROM AUTHOR]

Background and purpose: In recent years nanotechnology has a significant impact on various fields of human life, especially in pharmaceutical and medical needs. Some biopolymers such as chitosan which is also biocompatible are low cost and abundantly found, so, their application for vaccine production is cost benefit. Trimethyl chitosan is a deacetylated derivative of chitosan that could be used to increase the induction of immune response. In this study, trimethyl chitosan nanoparticles containing tetanus protein were used to stimulate the immune system. Materials and methods: In this experimental study, synthesis of the tetanus toxoid loaded nanoparticles was done by ion gelation method. Physical features of the nanoparticles were investigated using scanning electron microscopy (SEM). The nanoparticles were then injected subcutaneously into mice. After the sampling process, the immune system stimulation was evaluated using indirect ELISA. Data was analyzed using one-way ANOVA and significance level of P< 0.05. Results: The purity of protein was confirmed by SDS-PAGE and encapsulated proteins were loaded up to 80 percent. ELISA results showed that the immune system was stimulated significantly compared with Freund adjuvant, and antibody titer increased. Conclusion: Tetanus toxoid loaded Trimethyl chitosan nanoparticles increase the stimulation of immune system and are more effective in comparison with Freund's adjuvant.

Graphical abstract Abstract Peptide-based vaccines have the potential to overcome the limitations of classical vaccines; however, their use is hampered by a lack of carriers and adjuvants suitable for human use. In this study, an efficient self-adjuvanting peptide vaccine delivery system was developed based on the ionic interactions between cationic trimethyl chitosan (TMC) and a peptide antigen coupled with synthetically defined anionic α-poly-(l -glutamic acid) (PGA). The antigen, possessing a conserved B-cell epitope derived from the group A streptococcus (GAS) pathogen and a universal T-helper epitope, was conjugated to PGA using cycloaddition reaction. The produced anionic conjugate formed nanoparticles (NP-1) through interaction with cationic TMC. These NP-1 induced higher systemic and mucosal antibody titers compared to antigen adjuvanted with standard mucosal adjuvant cholera toxin B subunit or antigen mixed with TMC. The produced serum antibodies were also opsonic against clinically isolated GAS strains. Further, a reduction in bacterial burden was observed in nasal secretions, pharyngeal surface and nasopharyngeal-associated lymphoid tissue of mice immunized with NP-1 in GAS challenge studies. Thus, conjugation of defined-length anionic polymer to peptide antigen as a means of formulating ionic interaction-based nanoparticles with cationic polymer is a promising strategy for peptide antigen delivery. Statement of Significance A self-adjuvanting delivery system is required for peptide vaccines to enhance antigen delivery to immune cells and generate systemic and mucosal immunity. Herein, we developed a novel self-adjuvanting nanoparticulate delivery system for peptide antigens by combining polymer-conjugation and complexation strategies. We conjugated peptide antigen with anionic α-poly-(l -glutamic acid) that in turn, formed nanoparticles with cationic trimethyl chitosan by ionic interactions, without using external crosslinker. On intranasal administration to mice, these nanoparticles induced systemic and mucosal immunity, at low dose. Additionally, nanoparticles provided protection to vaccinated mice against group A streptococcus infection. Thus, this concept should be particularly useful in developing nanoparticles for the delivery of peptide antigens. [ABSTRACT FROM AUTHOR]

The aim of the study was to encapsulate resveratrol (RV) in trimethyl chitosan (TMC) nanoparticles cross-linked with tripolyphosphate (TPP) and/or alginate to achieve controlled release and improved cellular uptake. TMC (degree of quaternization of 78%) was prepared by reacting purified chitosan with iodomethane. Three types of RV-loaded TMC nanoparticles were prepared: TMC-TPP (TP-NPs), TMC-alginate (TA-NPs), and TMC-alginate-TPP (TAP-NPs). TA-NPs and TAP-NPs showed lower particle size and encapsulation efficiency (EE), better distribution, and more sustained release than TP-NPs due to the high molecular weight and viscous property of alginate. Caco-2 cellular uptake of RV was improved by TMC nanoencapsulation, and TP-NPs showed the highest uptake due to its significantly higher EE. Compared with TAP-NPs, TA-NPs with higher positive surface charge showed higher cellular uptake. Moreover, Caco-2 cell growth-inhibiting activity of RV was significantly increased by TMC nanoencapsulation and TP-NPs showed the significantly highest activity with a good agreement with the permeability results. [ABSTRACT FROM AUTHOR]

Mucoadhesive drug delivery systems are desirable as they can increase the residence time of drugs at the site of absorption/action, provide sustained drug release and minimize the degradation of drugs in various body sites. Chitosan is a cationic polysaccharide that exhibits mucoadhesive properties and it has been widely used in the design of mucoadhesive dosage forms. However, its limited mucoadhesive strength and limited water-solubility at neutral and basic pHs are considered as two major drawbacks of its use. Chemical modification of chitosan has been exploited to tackle these two issues. In this review, we highlight the up-to-date studies involving the synthetic approaches and description of mucoadhesive properties of chitosan and chitosan derivatives. These derivatives include trimethyl chitosan, carboxymethyl chitosan, thiolated chitosan, chitosan-enzyme inhibitors, chitosan-ethylenediaminetetraacetic acid (chitosan-EDTA), half-acetylated chitosan, acrylated chitosan, glycol chitosan, chitosan-catechol, methyl pyrrolidinone-chitosan, cyclodextrin-chitosan and oleoyl-quaternised chitosan. We have particularly focused on the effect of chemical derivatization on the mucoadhesive properties of chitosan. Additionally, other important properties including water-solubility, stability, controlled release, permeation enhancing effect, and in vivo performance are also described. [ABSTRACT FROM AUTHOR]

N,N,N-Trimethyl chitosan (TMC) is one chitosan derivative that, because of its improved solubility, has been studied for industrial and pharmaceutic applications. Conventional methods for the synthesis of TMC involve the use of highly toxic and harmful reagents, such as methyl iodide and dimethyl sulfate (DMS). Although the methylation of dimethylated chitosan to TMC by dimethyl carbonate (DMC, a green and benign methylating agent) was reported recently, it involved a formaldehyde-based procedure. In this paper we report the single-step synthesis of TMC from chitosan using DMC in an ionic liquid. The TMC synthesised was characterised by 1H NMR spectroscopy and a functionally meaningful degree of quaternisation of 9% was demonstrated after a 12-h reaction time.

The presence of several organic contaminants in the environment and aquatic compartments has been a matter of great concern in the recent years. To tackle this problem, new sustainable and cost-effective technologies are needed. Herein we describe magnetic biosorbents prepared from trimethyl chitosan (TMC), which is a quaternary chitosan scarcely studied for environmental applications. Core@shell particles comprising a core of magnetite (Fe3O4) coated with TMC/siloxane hybrid shells (Fe3O4@SiO2/SiTMC) were successfully prepared using a simple one-step coating procedure. Adsorption tests were conducted to investigate the potential of the coated particles for the magnetically assisted removal of the antibiotic sulfamethoxazole (SMX) from aqueous solutions. It was found that TMC-based particles provide higher SMX adsorption capacity than the counterparts prepared using pristine chitosan. Therefore, the type of chemical modification introduced in the chitosan type precursors used in the surface coatings has a dominant effect on the sorption efficiency of the respective final magnetic nanosorbents.

Purpose: To formulate trimethyl chitosan-functionalized retinoic acid-encapsulated solid lipid nanoparticles for the effective treatment of glioma. Methods: Retinoic acid-loaded solid lipid nanoparticles (R-SLNs) were prepared using homogenization followed by sonication. R-SLN surfaces were functionalized electrostatically with trimethyl chitosan as a nanocarrier (TR-SLNs) with enhanced anti-cancer activity. They were evaluated by dynamic light scattering (DLS), scanning electron microscopy, in vitro drug release, and cell cytotoxicity and apoptosis studies. Results: Morphological images showed spherical and uniformly dispersed nanoparticles. A sustained monophasic release pattern was observed throughout the study period. Furthermore, the anti-cancer effect of TR-SLNs was demonstrated by increased cell killing activity compared with the free drug (p < 0.01); negligible cytotoxicity was observed with blank carriers. Apoptosis assay showed increased cell populations in early/late apoptotic and necrotic phases. Conclusion: This study showed the potential application of surface-modified solid lipid nanoparticles for the effective treatment of brain cancer. [ABSTRACT FROM AUTHOR]

Paclitaxel (PTX) conjugated trimethyl chitosan (TMC-PTX) and folic acid (FA) modified TMC-PTX (FA-TMC-PTX) were developed as polymer-drug conjugates for oral and intravenous delivery of PTX. As amphiphilic conjugates, TMC-PTX and FA-TMC-PTX containing approximately 11 wt% PTX could self-assemble into spherical nanoparticles with average sizes of 170 and 187 nm, respectively. The conjugates presented a sustained release of PTX and the release rate was positively correlated with the pH value of medium ranging from 1.2 to 7.4. TMC-PTX and FA-TMC-PTX possessed enhanced mucoadhesion compared with trimethyl chitosan, and promoted ex vivo intestinal transport of PTX in comparison to PTX solution by 15.5 and 18.8 folds, respectively. Hemolysis assessment confirmed the safety of TMC-PTX and FA-TMC-PTX, and FA modification alleviated protein adsorption of the conjugates. Prolonged blood retention and increased PTX accumulation in the tumor were achieved for orally and intravenously administered conjugates. In H22 tumor-bearing mice, TMC-PTX delivered via oral or intravenous route showed superior tumor retardation and survival rate compared with intravenously injected PTX, and FA-TMC-PTX further enhanced the antitumor efficacy. Overall, the trimethyl chitosan based drug conjugates may have potential applications as a promising candidate for cancer therapy. Statement of Significance In the current study, PTX conjugated trimethyl chitosan (TMC-PTX) and folic acid (FA) modified TMC-PTX (FA-TMC-PTX) were developed as the polymer-drug conjugates for oral and intravenous delivery of PTX. By exploiting advantages with respect to improved solubility of drugs, controlled release behavior of covalently linked drugs, and enhanced targeting effect towards tumors, improved tumor growth inhibition efficacy and prolonged survival time were achieved for TMC-PTX as compared with free PTX, and FA modification further enhanced the in vivo antitumor efficacy. Overall, the self-assembled nanoplatform of trimethyl chitosan based drug conjugates may have potential applications as a promising candidate for tumor therapy via different administration routes. [ABSTRACT FROM AUTHOR]

Neuron-targeted gene delivery is a promising strategy to treat peripheral neuropathies. Here we propose the use of polymeric nanoparticles based on thiolated trimethyl chitosan (TMCSH) to mediate targeted gene delivery to peripheral neurons upon a peripheral and minimally invasive intramuscular administration. Nanoparticles were grafted with the non-toxic carboxylic fragment of the tetanus neurotoxin (HC) to allow neuron targeting and were explored to deliver a plasmid DNA encoding for the brain-derived neurotrophic factor (BDNF) in a peripheral nerve injury model. The TMCSH-HC/BDNF nanoparticle treatment promoted the release and significant expression of BDNF in neural tissues, which resulted in an enhanced functional recovery after injury as compared to control treatments (vehicle and non-targeted nanoparticles), associated with an improvement in key pro-regenerative events, namely, the increased expression of neurofilament and growth-associated protein GAP-43 in the injured nerves. Moreover, the targeted nanoparticle treatment was correlated with a significantly higher density of myelinated axons in the distal stump of injured nerves, as well as with preservation of unmyelinated axon density as compared with controls and a protective role in injury-denervated muscles, preventing them from denervation. These results highlight the potential of TMCSH-HC nanoparticles as non-viral gene carriers to deliver therapeutic genes into the peripheral neurons and thus, pave the way for their use as an effective therapeutic intervention for peripheral neuropathies. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effect of molecular weight (MW) of chitosan and the degree ofquaternization (DQ) of trimethyl chitosan (TMC) on the formation of particles. The amount of tripolyphosphate (TPP) wasvaried in order to optimize the preparation condition of particles. Particle size, zeta potential, loading efficiency (LE) of ovalbumin(OVA), a model antigen, and OVA release profiles were also investigated in order to select the best systems for oralvaccine delivery. The results showed that the amount of TPP added has an effect on the ability of chitosan and TMC polymerto form particles. The formation of chitosan particles required a higher amount of TPP than that of TMC particles. Using thesame amount of TPP, the MW of chitosan did not have an effect on particle formation whereas the DQ of TMC had. Dependingon the amount of TPP, the size of particles prepared from chitosan and their TMC were in the range of 0.5-2.3 m andtheir positive charges were in the range of 3-48 mV. Adding the same amount of TPP, the size of the chitosan particles waslarger than that of their respective TMC particles. The size of the TMC particles was decreased with increasing of DQ. Thezeta potential of the TMC particles was higher than that of their starting chitosan particles and it increased with increasingDQ. The loading efficiency (LE) of OVA onto the TMC particles was charge-dependent. MW did not affect the LE of chitosanparticles. The OVA release from the particles prepared depended on the solubility and loading capacity of the particles.

Background and purpose: In recent years nanotechnology has a significant impact on various fields of human life, especially in pharmaceutical and medical needs. Some biopolymers such as chitosan which is also biocompatible are low cost and abundantly found, so, their application for vaccine production is cost benefit. Trimethyl chitosan is a deacetylated derivative of chitosan that could be used to increase the induction of immune response. In this study, trimethyl chitosan nanoparticles containing tetanus protein were used to stimulate the immune system. Materials and methods: In this experimental study, synthesis of the tetanus toxoid loaded nanoparticles was done by ion gelation method. Physical features of the nanoparticles were investigated using scanning electron microscopy (SEM). The nanoparticles were then injected subcutaneously into mice. After the sampling process, the immune system stimulation was evaluated using indirect ELISA. Data was analyzed using one-way ANOVA and significance level of P< 0.05. Results: The purity of protein was confirmed by SDS-PAGE and encapsulated proteins were loaded up to 80 percent. ELISA results showed that the immune system was stimulated significantly compared with Freund adjuvant, and antibody titer increased. Conclusion: Tetanus toxoid loaded Trimethyl chitosan nanoparticles increase the stimulation of immune system and are more effective in comparison with Freund's adjuvant. [ABSTRACT FROM AUTHOR]

By using imaging flow cytometry as a powerful statistical high-throughput technique we investigated the impact of degradation on the biological performance of trimethyl chitosan (TMC)-based nanoparticles (NPs). In order to achieve high transfection efficiencies, a precise balance between NP stability and degradation must occur. We altered the biodegradation rate of the TMC NPs by varying the degree of acetylation (DA) of the polymer (DA ranged from 4 to 21%), giving rise to NPs with different enzymatic degradation profiles. While this parameter did not affect NP size, charge or ability to protect plasmid DNA, NPs based on TMC with an intermediate DA (16%) showed the highest transfection efficiency. Subsequently, by means of a single quantitative technique, we were able to follow, for each tested formulation, major steps of the NP-mediated gene delivery process – NP cell membrane association, internalization and intracellular trafficking, including plasmid DNA transport towards the nucleus. NP cytotoxicity was also possible to determine by quantification of cell apoptosis. Overall, the obtained data revealed that the biodegradation rate of these NPs affects their intracellular trafficking and, consequently, their efficiency to transfect cells. Thus, one can use the polymer DA to modulate the NPs towards attaining different degradation rates and tune their bioactivity according to the desired application. Furthermore, this novel technical approach revealed to be a valuable tool for the initial steps of nucleic acid vector design. Statement of Significance By changing the biodegradation rate of trimethyl chitosan-based nanoparticles (NPs) one was able to alter the NP ability to protect or efficiently release DNA and consequently, to modulate their intracellular dynamics. To address the influence of NP degradation rate in their transfection efficiency we took advantage of imaging flow cytometry, a high-throughput bioimaging technique, to unravel some critical aspects about NP formulation such as the distinction between internalized versus cell-associated/adsorbed NP, and even explore NP intracellular localization. Overall, our work provides novel information about the importance of vector degradation rate for gene delivery into cells, as a way to tune gene expression as a function of the desired application, and advances novel approaches to optimize nanoparticle formulation. [ABSTRACT FROM AUTHOR]

In this study, the use of trimethylchitosan (TMC), by higher solubility in comparison with chitosan, in alginate/chitosan nanoparticles containing cationic β-cyclodextrin polymers (CPβCDs) has been studied, with the aim of increasing insulin uptake by nanoparticles. Firstly, TMCs were synthesized by iodomethane, and CPβCDs were synthesized within a one-step polycondensation reaction using choline chloride (CC) and epichlorohydrine (EP). Insulin-CβCDPs complex was prepared by mixing 1:1 portion of insulin and CPβCDs solutions. Then, nanoparticles prepared in a three-step procedure based on the iono-tropic pregelation method. Nanoparticles screened using experimental design and Placket Burman methodology to obtain minimum size and polydispercity index (pdI) and the highest entrapment efficiency (EE). CPβCDs and TMC solution concentration and pH and alginate and calcium chloride solution concentrations are found as the significant parameters on size, PdI, and EE. The nanoparticles with proper physicochemical properties were obtained; the size, PdI, and EE% of optimized nanoparticles were reported as 150.82 ± 21 nm, 0.362 ± 0.036, and 93.2% ± 4.1, respectively. The cumulative insulin release in intestinal condition achieved was 50.2% during 6 h. By SEM imaging, separate, spherical, and nonaggregated nanoparticles were found. In the cytotoxicity studies on Caco-2 cell culture, no significant cytotoxicity was observed in 5 h of incubation, but after 24 h of incubation, viability was decreased to 50% in 0.5 mμ of TMC concentration. Permeability studies across Caco-2 cells had been carried out, and permeability achieved in 240 min was 8.41 ± 0.39%, which shows noticeable increase in comparison with chitosan nanoparticles. Thus, according to the results, the optimized nanoparticles can be used as a new insulin oral delivery system. [ABSTRACT FROM AUTHOR]

In this study, the interaction of fluorescein isothiocyanate functionalized bovine serum albumin (FITC-BSA) with cellulose surfaces decorated with trimethyl chitosan (TMC) is investigated. Two types of TMC, one exhibiting a lower and one with a higher degree of cationization are used for protein adsorption. The adsorption is carried out at different pH values and concentrations of the protein solution. The amount, morphology and wettability of FITC-BSA coating on TMC/cellulose films are determined using quartz crystal microbalance with dissipation (QCM-D), atomic force microscopy, fluorescence microscopy and contact angle measurements. A lower pH and higher concentration of protein solution resulted in a greater amount of irreversibly adsorbed material owing to the reduced solubility and minimized electrostatic repulsion. A maximum adsorption of protein is observed on cellulose surfaces functionalized with TMC carrying a higher degree of cationization compared to TMC with a lower degree of cationization and pure cellulose surfaces at all applied concentrations and pH values. BSA is a commonly used model protein and is applied in this study to better understand its interaction with cationically rendered cellulose surfaces. Such knowledge is essential for creation of multifunctional polysaccharide-based biomaterials. [ABSTRACT FROM AUTHOR]

Abstract: Quaternary N-(2-(N,N,N-tri-alkyl ammoniumyl and 2-pyridiniumyl) acetyl) derivatives of chitosan polymer, chitooligomer, and glucosamine (monomer) were synthesized for the purpose of investigating the structure activity relationship (SAR) for the antibacterial effect. Novel methods were used in the synthesis. The final chitosan and chitooligomer derivatives could thus be obtained in two steps without prior protection of the hydroxyl groups. However, in order to obtain chitosan derivatives with the bulky N,N-dimethyl-N-dodecyl- and N,N-dimethyl-N-butyl side chains three steps were needed, starting from 3,6-O-di-tert-butyldimethylsilyl chitosan (3,6-O-di-TBDMS chitosan) as the key intermediate. The quaternary ammoniumyl acetyl derivatives of glucosamine were synthesized from glucosamine or tetra-O-acetylglucosamine. N,N,N-trimethyl chitosan (TMC) was used as reference compound for investigation of antibacterial activity. Clinical Laboratory Standard Institute (CLSI) protocols were used to determine MIC and MLC for activity against clinically important Gram-positive strains Staphylococcus aureus (ATCC 25923), and S. aureus (MRSA) (ATCC 43300), and Gram-negative strains of Escherichia coli (ATCC 25922), P. aeriginosa (ATCC 27853) and Enterococcus facialis (ATCC 29212). The MIC values for the compounds ranged from 8 to ⩾8192mg/L. In general the N-(2-(N,N-dimethyl-N-dodecyl ammoniumyl) acetyl) derivatives of chitooligomer and glucosamine monomer were more active against bacteria than derivatives with shorter alkyl chains. In contrast the N-(2-(N,N-dimethyl-N-dodecyl ammoniumyl) acetyl) derivatives of chitosan were less active than derivatives with N-(2-N,N,N-trimetylammoniumyl) acetyl or N-(2-(N-pyridiniumyl) acetyl) quaternary moiety. N,N,N-trimethyl chitosan (TMC) was the most active compound in this study. [Copyright &y& Elsevier]

The potential of palladium has been scantily explored in biomedical applications. In the present study, palladium nanoparticles (PdNPs) were synthesized and were successfully coated with trimethyl-chitosan (TMC) to improve their biocompatibility. Coating with TMC improved the nanoparticle accumulation in MDAMB231 breast cancer cells, compared to nanoparticles coated with native chitosan. The TMC coated palladium nanoparticles (TMC/PdNPs) exhibited good biocompatibility and physiological stability, as compared to the plain(uncoated) PdNPs. TMC coated PdNPs resulted in photothermal therapeutic effect, when irradiated with a near-infrared (NIR) laser having the wavelength of 808-nm. The TMC/PdNPs resulted in good cytotoxic effect upon laser treatment in both, 2D monolayers and 3D spheroids of MDAMB231 cells, the latter mimicking the tumor microenvironment. These results clearly indicated that TMC/PdNPs acted as ideal photothermal agents for anti-cancer therapy in combination with a non-invasive near-infrared laser. [Display omitted] • Trimethyl chitosan (TMC) coated palladium nanoparticles (TMC/PdNPs) were fabricated. • TMC acted as stabilizing agent during auto-assembly of palladium cores. • TMC/PdNPs exhibited better cell-adhesion property compared to chitosan PdNPs. • TMC/PdNPs generated a highly photothermal effect upon irradiation. • TMC/PdNPs exhibited excellent photothermal efficiency on 2D and 3D cancer cells. [ABSTRACT FROM AUTHOR]

Abstract: A thermoresponsive copolymer, trimethyl chitosan-g-poly(N-isopropylacrylamide) (TMC-g-PNIPAAm), was synthesized by coupling PNIPAAm-COOH to TMC. Their molecular structures were characterized by 1HNMR. The lower critical solution temperature (LCST) of TMC-g-PNIPAAm in PBS was measured as 32°C by dynamic light scattering (DLS) and UV–vis spectroscopy, regardless of the grafting ratios. Upon mixing with DNA, TMC/DNA particles were formed, whose size and morphology were investigated by DLS and transmission electron microscopy, respectively. The particle size ranged from 200 to 900nm depending on the N/P ratio and was less influenced by the temperature variation. The majority of the particles have spherical morphology. The zeta potentials of these particles were increased along with the N/P ratio. At a given N/P ratio, the zeta potentials were almost constant at 25°C regardless of the existence of serum proteins. However, the values were significantly decreased at 37°C in a solution containing serum protein. The affinity between DNA and TMC was examined by ethidium bromide competitive binding assay. TMC-g-PNIPAAm has stronger ability to combine with DNA at 40°C when the PNIPAAm chain is collapsed. Gel electrophoresis results reveal that the vectors/DNA complexes can be formed regardless of the incubation temperature. HEK293 cell line was chosen as a model to study cellular uptake of the TMC-g-PNIPAAm/DNA particles, gene transfection and cytotoxicity. The grafting of PNIPAAm will not affect cellular uptake of the particles at 37°C. The level of gene transfection could be thermally controlled. By using a temperature variation protocol, i.e. incubation of the cultured cells at 25°C for a while, the gene transfection efficiency was significantly improved. Finally, the optimized gene transfection efficiency achieved by TMC-g-PNIPAAm is comparable to Lipofectamine 2000. No obvious cytotoxicity was detected for the TMC-g-PNIPAAm/DNA particles. These results suggest that TMC-g-PNIPAAm is an effective thermoresponsive gene carrier with minimal cytotoxicity, which has great promise for practical applications. [Copyright &y& Elsevier]

Abstract: PEGylated trimethyl chitosan (TMC) copolymers were synthesized in an attempt to both increase the solubility of chitosan in water, and improve the biocompatibility of TMC. A series of copolymers with different degrees of substitution were obtained by grafting activated poly(ethylene glycol)s (PEG) of different MW onto TMC via primary amino groups. Structure of the copolymers was characterized using 1H, 13C NMR spectroscopy and GPC. Solubility experiments demonstrated that PEG-g-TMC copolymers were completely water-soluble over the entire pH range of 1–14 regardless of the PEG MW, even when the graft density was as low as 10%. Using the methyl tetrazolium (MTT) assay, the effect of TMC molecular weight, PEGylation ratio, PEG and TMC molecular weight in the copolymers, and complexation with insulin on the cytotoxicity of TMC was examined, and IC50 values were calculated with L929 cell line. All polymers exhibited a time- and dose-dependent cytotoxic response that increased with molecular weight. PEGylation can decrease the cytotoxicity of TMC to a great extent in the case of low molecular weight TMCs. According to the cytotoxicity results, PEG 5kDa is superior for PEGylation when compared to PEG 550Da at similar graft ratios. Complexation with insulin further increased cell viability. In addition, Lactate dehydrogenase (LDH) assays were performed to quantify the membrane-damaging effects of the copolymers, which is in line with the conclusion drawn from MTT assay. Moreover, the safety of the copolymers was corroborated by observing the morphological change of the cells with inverted phase contrast microscopy. Based upon these results PEG-g-TMC merits further investigations as a drug delivery vehicle. [Copyright &y& Elsevier]

The purpose of this research was to prepare poly-(ε-caprolactone) (PCL) particles by an emulsion-diffusion-evaporation method using a blend of poly-(vinyl alcohol) and chitosan derivatives as stabilizers. The chitosan derivatives used were chitosan hydrochloride and trimethyl chitosans (TMC) with varying degrees of quaternization. Particle characteristics-size, zeta potential, surface morphology, cytotoxicity, and transfection efficiency-were investigated. The developed method yields PCL nanoparticles in the size range of 250 to 300 nm with a positive surface charge (2.5 to 6.8 mV). The cytotoxicity was found to be moderate and virtually independent of the stabilizers' concentration with the exception of the highly quaternized TMC (degree of substitution 66%) being significantly more toxic. In immobilization experiments with gel electrophoresis, it could be shown that these cationic nanoparticles (NP) form stable complexes with DNA at a NP:DNA ratio of 3:1. These nanoplexes showed a significantly higher transfection efficiency on COS-1 cells than naked DNA. [ABSTRACT FROM AUTHOR]

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most common pharmaceuticals used worldwide. They are widely detected in natural waters due to their persistence in wastewater treatment, and their removal is desirable in wastewater management. As a contribution to tackle this challenge, this study explores magnetic quaternary chitosan-based nanosorbents for the effective magnetically assisted removal of three NSAIDs (diclofenac, naproxen, and ketoprofen) from water. Toward this goal, silane groups were grafted onto the backbone of trimethyl chitosan through the reaction with an epoxide functionalized silane. Once silanized, the modified chitosan was employed to coat Fe3O4 nanoparticles. The prepared materials were characterized using FTIR spectroscopy and solid-state 29Si and 13C NMR spectroscopy, which confirmed the encapsulation of Fe3O4 nanoparticles with a hybrid siliceous material enriched in trimethyl chitosan. The effect of the initial NSAIDs concentration, pH, and contact time in the adsorption behavior was investigated. The kinetic data were well described by the pseudo-second-order kinetic model, indicating a chemisorption mechanism. The maximum adsorption capacities estimated from the Langmuir model were 188.5 mg/g (0.5925 mmol/g), 438.1 mg/g (1.7371 mmol/g), and 221.5 mg/g (0.8710 mmol/g) for diclofenac, naproxen, and ketoprofen, respectively. These adsorption capacities are higher than those of most reported sorbents, indicating the potential of these biosorbents to remove the selected NSAIDs using low-energy magnetically assisted separation. [ABSTRACT FROM AUTHOR]