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Background Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects 10 to 20% of children and between 2 and 15% of the adults in Western Europe. Since 2000, therapeutic clothing or functional textiles based on silver or chitosan as antibacterial agents were introduced for AD. These agents aim to reduce skin colonization with Staphylococcus ( S .) aureus . Increased colonization with S. aureus is correlated with increased AD severity. The antimicrobial effects of silver and chitosan have been demonstrated before. At this point, there is insufficient evidence for the effectiveness of antibacterial therapeutic clothing in patients with AD. Methods This is a pragmatic randomized controlled double-blind multi-center trial comparing the effectiveness of antibacterial therapeutic clothing based on silver or chitosan as compared with non-antibacterial therapeutic clothing in patients with moderate to severe AD. A total of 165 participants, aged 0 to 80, diagnosed with moderate to severe AD are included. The study is performed in the Erasmus MC University Medical Center, University Medical Center Groningen, University Medical Center Utrecht, Amsterdam University Medical Centers, and St. Antonius Hospital Nieuwegein. Patients will be randomized 1:1:1 into one of the three intervention groups: group A will receive therapeutic clothing without antimicrobial agents, group B will receive microbial growth reducing therapeutic clothing based on chitosan, and group C will receive antimicrobial clothing based on silver. All therapeutic clothing is to be worn at night during the 12-month intervention period. Usual care is continued. The primary objective is to assess the effectiveness of antibacterial clothing (silver and chitosan group) as compared to non-antibacterial clothing assessed with the Eczema Area and Severity Index at 12 months compared to baseline. Secondary outcomes include between-group differences in physician- and patient-reported outcome measures, topical therapy use, S. aureus skin colonization, and safety. Data will be collected at baseline and after 1 month, 3 months, 6 months, and 12 months. A cost-effectiveness analysis will be performed. Discussion This trial will provide data on the effectiveness, cost-effectiveness, and safety of antibacterial therapeutic clothing for patients with AD. Trial registration ClinicalTrials.gov NCT04297215. Registered on 5 March 2020

Postoperative bleeding and adhesion formation are the two most common complications after endoscopic sinus surgery (ESS). Continued bleeding risks airway compromise from the inhalation of blood clots and from the aspiration of blood-stained vomitus. Additionally, adhesion formation is the most common reason for patients requiring revision surgery. This study aimed to determine the efficacy of a novel chitosan/dextran (CD) gel on hemostasis and wound healing after ESS. A randomized controlled trial was performed involving 40 patients undergoing ESS for chronic rhinosinusitis. Immediately after surgery a baseline Boezaart Surgical Field Grading Scale was taken. Computer randomization was performed with one side receiving CD gel and the other side receiving no treatment (control). Boezaart bleeding scores were then calculated for each side every 2 minutes. Patient's endoscopic features of wound healing were assessed at 2, 6, and 12 weeks after surgery. CD gel achieved rapid hemostasis with the mean time to hemostasis at 2 minutes (95% CI, 2-4 minutes) compared with 10 minutes (95% CI, > or =6 minutes) for the control (p < 0.001). There were significantly less adhesions at all time points with CD gel versus control: 2 versus 18 at 2 weeks (p < 0.001), 3 versus 16 at 6 weeks (p < 0.001), and 2 versus 12 at 3 months (p < 0.001). There was no significant difference between CD gel and control with respect to crusting, mucosal edema, infection, or granulation tissue formation. CD gel is rapidly hemostatic immediately after ESS and prevents adhesion formation, addressing two of the most common complications of sinus surgery.

Chitosan treatment results in significantly lower serum low density lipoprotein (LDL) cholesterol concentrations. To assess the working mechanisms of chitosan, we measured serum surrogate markers of cholesterol absorption (campesterol, sitosterol, cholestanol), synthesis (lathosterol, lanosterol, desmosterol), and degradation to bile acids (7α-hydroxy-cholesterol, 27-hydroxy-cholesterol), corrected for cholesterol concentration (R_sterols). Over 12 weeks, 116 obese subjects (Body Mass Index, BMI 31.7, range 28.1–38.9 kg/m2) were studied under chitosan (n = 61) and placebo treatments (n = 55). The participants were briefly educated regarding improvement of nutrition quality and energy expenditure. Daily chitosan intake was 3200 mg. Serum LDL cholesterol concentration decreased significantly more (p = 0.0252) under chitosan (−8.67 ± 18.18 mg/dL, 5.6%) than under placebo treatment (−1.00 ± 24.22 mg/dL, 0.9%). This reduction was not associated with the expected greater decreases in markers of cholesterol absorption under chitosan treatment. Also, increases in markers of cholesterol synthesis and bile acid synthesis under chitosan treatment were not any greater than under placebo treatment. In conclusion, a significant selective reduction of serum LDL cholesterol under chitosan treatment is neither associated with a reduction of serum surrogate markers of cholesterol absorption, nor with increases of markers for cholesterol and bile acid synthesis.

Chitosan is widely used in the biomedical field due its chemical and pharmacological properties. However, intake of chitosan results in renal tissue accumulation of chitosan and promotes an increase in calcium excretion. On the other hand, the effect of chitosan on the formation of calcium oxalate crystals (CaOx) has not been described. In this work, we evaluated the antioxidant capacity of chitosan and its interference in the formation of CaOx crystals in vitro. Here, the chitosan obtained commercially had its identity confirmed by nuclear magnetic resonance and infrared spectroscopy. In several tests, this chitosan showed low or no antioxidant activity. However, it also showed excellent copper-chelating activity. In vitro, chitosan acted as an inducer mainly of monohydrate CaOx crystal formation, which is more prevalent in patients with urolithiasis. We also observed that chitosan modifies the morphology and size of these crystals, as well as changes the surface charge of the crystals, making them even more positive, which can facilitate the interaction of these crystals with renal cells. Chitosan greatly influences the formation of crystals in vitro, and in vivo analyses should be conducted to assess the risk of using chitosan.

Newcastle disease (ND) is a highly contagious viral disease of poultry caused by pathogenic strains of the Newcastle disease virus (NDV). Live NDV vaccines are administered by drinking water, eyedrops or coarse aerosol spray. To further enhance mucosal immune responses, chitosan nanoparticles were developed for the mucosal delivery of a live NDV vaccine. A lentogenic live-virus vaccine (strain LaSota) against NDV encapsulated in chitosan nanoparticles were developed using an ionic crosslinking method. Chitosan nanoparticles containing the lentogenic live-virus vaccine against NDV (NDV-CS-NPs) were produced with good morphology, high stability, a mean diameter of 371.1 nm, an encapsulation rate of 77% and a zeta potential of +2.84 mV. The Western blotting analysis showed that NDV structural proteins were detected in NDV-CS-NPs. The virus release assay results of NDV-CS-NPs indicated that NDV was released from NDV-CS-NPs. Chickens immunized orally or intranasally with NDV-CS-NPs were fully protected whereas one out of five chickens immunized with the LaSota live NDV vaccine and three out of five chickens immunized with the inactivated NDV vaccine were dead after challenge with the highly virulent NDV strain F48E9. NDV-CS-NPs induced better protection of immunized specific pathogen free chickens compared to the live NDV vaccine strain LaSota and the inactivated NDV vaccine. This study lays a foundation for the further development of mucosal vaccines and drugs encapsulated in chitosan nanoparticles.

Chitosan is a natural polymer with applications in agriculture, which causes plasma membrane permeabilisation and induction of intracellular reactive oxygen species (ROS) in plants. Chitosan has been mostly applied in the phylloplane to control plant diseases and to enhance plant defences, but has also been considered for controlling root pests. However, the effect of chitosan on roots is virtually unknown. In this work, we show that chitosan interfered with auxin homeostasis in Arabidopsis roots, promoting a 2–3 fold accumulation of indole acetic acid (IAA). We observed chitosan dose-dependent alterations of auxin synthesis, transport and signalling in Arabidopsis roots. As a consequence, high doses of chitosan reduce WOX5 expression in the root apical meristem and arrest root growth. Chitosan also propitiates accumulation of salicylic (SA) and jasmonic (JA) acids in Arabidopsis roots by induction of genes involved in their biosynthesis and signalling. In addition, high-dose chitosan irrigation of tomato and barley plants also arrests root development. Tomato root apices treated with chitosan showed isodiametric cells respect to rectangular cells in the controls. We found that chitosan causes strong alterations in root cell morphology. Our results highlight the importance of considering chitosan dose during agronomical applications to the rhizosphere.

Injectable thermo-sensitive chitosan hydrogels have recently been developed for the use of submucosal fluids in endoscopic submucosal dissections (ESD). This study aimed to investigate the efficacy and safety of chitosan hydrogels during ESD. Submucosal fluids were administered as follows: 0.9% normal saline (NS), 0.4% hyaluronic acid (HA) and chitosan/β-glycerophosphate (CS/GP) hydrogel. Each solution was administered twice into the stomach and colon of a pig, with a total of 72 ESD procedures performed on 12 pigs. The injected volume and procedure-related parameters were recorded and analyzed. ESDs that created ulcers after 7 days were histologically compared. All ESD specimens were resected en bloc. The total injected volumes during ESD of the stomach (NS, 16.09±3.27 vs. HA, 11.17±2.32 vs. CS/GP, 9.44±2.33; p<0.001) and colon (NS, 9.17±1.80 vs. HA, 6.67±1.50 vs. CS/GP, 6.75±1.57; p = 0.001) were significantly different. Hydrogel showed significant differences from normal saline in terms of fluid power (mm 2 /vol; NS, 35.70±9.00 vs. CS/GP 57.48±20.77; p = 0.001) and consumption rate (vol/min; NS, 2.59±0.86 vs. CS/GP, 1.62±0.65; p = 0.013) in the stomach. Histological examination revealed preserved muscularis propria, although the chitosan hydrogel resulted in a partial inflammatory response, with a hypertrophied submucosal layer. Chitosan hydrogel was found to be superior to normal saline, with an efficacy similar to that of hyaluronic acid. Nonetheless, long-term histological changes should be evaluated before clinical implementation.

The study was conducted to investigate the promoted immune response to ovalbumin in mice by chitosan nanoparticles (CNP) and its toxicity. CNP did not cause any mortality or side effects when mice were administered subcutaneously twice with a dose of 1.5 mg at 7-day intervals. Institute of Cancer Research (ICR) mice were immunized subcutaneously with 25 µg ovalbumin (OVA) alone or with 25 µg OVA dissolved in saline containing Quil A (10 µg), chitosan (CS) (50 µg) or CNP (12.5, 50 or 200 µg) on days 1 and 15. Two weeks after the secondary immunization, serum OVA-specific antibody titers, splenocyte proliferation, natural killer (NK) cell activity, and production and mRNA expression of cytokines from splenocytes were measured. The serum OVA-specific IgG, IgG1, IgG2a, and IgG2b antibody titers and Con A-, LPS-, and OVA-induced splenocyte proliferation were significantly enhanced by CNP (P < 0.05) as compared with OVA and CS groups. CNP also significantly promoted the production of Th1 (IL-2 and IFN-γ) and Th2 (IL-10) cytokines and up-regulated the mRNA expression of IL-2, IFN-γ and IL-10 cytokines in splenocytes from the immunized mice compared with OVA and CS groups. Besides, CNP remarkably increased the killing activities of NK cells activity (P < 0.05). The results suggested that CNP had a strong potential to increase both cellular and humoral immune responses and elicited a balanced Th1/Th2 response, and that CNP may be a safe and efficacious adjuvant candidate suitable for a wide spectrum of prophylactic and therapeutic vaccines.

Background Chitosan mouthwash has antimicrobial and antiplaque properties with lower cytotoxicity than many conventional mouthwashes. Given the well-known side effects of chlorhexidine, particularly tooth discoloration, this study aimed to compare enamel discoloration caused by chitosan, chlorhexidine, and chitosan-chlorhexidine mouthwashes, and to assess whether chitosan-based formulations could be a suitable alternative with fewer adverse effects. Materials and methods In this in vitro study, 45 extracted premolar teeth, obtained for orthodontic reasons and free from structural defects, cracks, restorations, or visible caries, were randomly allocated into three groups of 15 samples each (chitosan, chlorhexidine, and chitosan-chlorhexidine). The teeth were first cleaned with prophylaxis paste and rubber cups. After baseline color measurement of the buccal surface using a spectrophotometer, the first group was immersed in 0.5% chitosan solution, the second in 0.2% chlorhexidine mouthwash, and the third in a combination of 0.5% chitosan and 0.2% chlorhexidine solution for 24 h. Solutions were stirred every three hours to ensure homogeneity. Finally, the buccal surface color was reassessed with the spectrophotometer, and the color change (ΔE) was calculated. Data were analyzed using SPSS version 26, employing one-way ANOVA and Bonferroni post hoc tests. Results The mean color change (ΔE) in the chitosan group (3.14 ± 1.86) was significantly higher than in the chitosan-chlorhexidine group (1.74 ± 0.88) and the chlorhexidine group (1.78 ± 0.58) (One-way ANOVA, p  = 0.004). Pairwise comparisons using the Bonferroni test showed significant differences between the chitosan and chitosan-chlorhexidine groups ( p  = 0.010) and between the chitosan and chlorhexidine groups ( p  = 0.013). No significant difference was observed between the chitosan-chlorhexidine and chlorhexidine groups ( p  = 0.999). Conclusion Enamel discoloration caused by chitosan mouthwash is more than chlorhexidine and chitosan-chlorhexidine mouthwashes. Chitosan-chlorhexidine mouthwash revealed discoloration effects similar to those of chlorhexidine, indicating its potential as a substitute for traditional chlorhexidine, providing improved antimicrobial and antiplaque benefits while causing comparable or reduced discoloration.

One of the important routes of drug administration for localized delivery of contraceptives and cervical cancer treatment agents is vaginal canal. Due to the low pH of vagina, a pH-responsive drug delivery system was developed. This hydrogel was synthesized based on a mucoadhesive biopolymer, chitosan (CS), that promotes the interaction between the hydrogel and mucosal surface of the vagina, potentially increasing the residence time of the system. This injectable hydrogel was formed via acid-labile Schiff-base linkages between free amine groups and aldehyde functionalities on modified chitosan. A novel approach was taken to add aldehyde functionalities to chitosan using a two-step reaction. Two types of slow and fast degrading hydrogels were prepared and loaded with iron (II) gluconate dihydrate, a non-hormonal spermicide, and doxorubicin hydrochloride, an anti-cancer drug. The release profiles of these drugs at different pH environments were assessed to determine the pH-dependent release mechanism. Mechanical properties, swell-ability and degradation rate of these matrices were studied. The cross-linking density of the hydrogel as well as pH changes played an important role in the characteristic of these hydrogels. The hydrogels degraded faster in lower pH, while the hydrogel with lower cross-linking density showed longer gelation time and faster degradation rate compared to the gel with higher cross-linking density. In vitro cytotoxicity assessment of these hydrogels in 48 h indicated the non-toxic effect of these hydrogels toward mesenchymal stem cells (MSCs) in the test period.