Oral administration of PEDV-dissolved Alg-CS gel induces high and sustained mucosal immunity in mice.

Porcine epidemic diarrhea (PED) is a serious disease in piglets that leads to high mortality. An effective measure that provides higher IgA levels in the intestine and milk is required to decrease losses. Porcine epidemic diarrhea virus (PEDV) was dissolved in calcium alginate (Alg) and combined with chitosan (CS) via electrostatic interactions between cationic chitosan and anionic alginate to create a porous gel (Alg-CS+PEDV). The gel was used to immunize mice orally or in combination with subcutaneous injections of inactivated PEDV vaccine. At 12 and 24 days after immunization, levels of IgA and IgG in Alg-CS+PEDV were higher than with normal PEDV oral administration. At 24 days after immunization, the concentration of IFN-γ in Alg-CS+PEDV was higher than with normal PEDV oral administration. Furthermore, oral administration combining subcutaneous immunization induced higher levels of IgG and IgA than oral administration alone. Our study provides a new method for the preparation and administration of oral vaccines to achieve enhanced mucosal immunity against PEDV.

Strategies to prolong drug retention in solid tumors by aggregating Endo-CMC nanoparticles.

Developing a highly effective nano-drug delivery system with sufficient drug permeability and retention in tumors is still a major challenge for oncotherapy. Herein, a tumor microenvironment responsive, aggregable nanocarriers embedded hydrogel (Endo-CMC@hydrogel) was developed to inhibit the tumoral angiogenesis and hypoxia for enhanced radiotherapy. The antiangiogenic drug (recombinant human endostatin, Endo) loaded carboxymethyl chitosan nanoparticles (Endo-CMC NPs) was wrapped by 3D hydrogel to comprise the Endo-CMC@hydrogel. After peritumoral injection, the Endo-CMC NPs were released, invaded deeply into the solid tumor, and cross-linked with intratumoral calcium ions. The cross-linking process enabled these Endo-CMC NPs to form larger particles, leading to long retention in tumor tissue to minimize premature clearance. This Endo-CMC@hydrogel, integrating the abilities of good tumoral penetration, long retention of anti-drug, and alleviation of hypoxia in tumor tissue, greatly improved the therapeutic effect of radiotherapy. This work provides a proof-of-concept of tumor microenvironment-responding and an aggregable nano-drug delivery system as promising antitumor drug carriers for effective tumor therapy.

Sequentially sustained release of anticarcinogens for postsurgical chemoimmunotherapy.

Postsurgical treatment is of great importance to combat tumor recurrence and metastasis. Anti-CD47 antibodies (aCD47) can block the CD47-signal regulatory protein-alpha (CD47-SIRPα) pathway to restore immunity. Here, an in-situ gel implantation was engineered by crosslinking chitosan (CS) and pullulan (Pul) for postsurgical treatment. A highly selected chemotherapeutic, cyclopamine (Cyc), encapsulated in liposomes (Cyc-Lip) was co-loaded with aCD47 in gels for chemoimmunotherapy. Importantly, a sequential drug release kinetics can be achieved. Nanotherapeutics were confirmed to be released prior to aCD47 in a burst-release manner, which was benefit for immediately killing residual tumor cells followed by releasing tumor antigens. Meanwhile, aCD47 was released in a sustained-release manner to restore macrophage functions and exert anti-tumor immune responses. Afterwards, the efficacy of in-situ chemoimmunotherapy was confirmed on 4T1 mouse breast cancer models, which could not only efficiently augment anti-tumor effect to inhibit tumor recurrence but also establish a long-term immune memory to combat tumor metastasis.

Uso de quitina e quitosana como adsorventes de amônia de efluentes aquícolas: revisão de literatura / Use of chitin and quitosan as adsorvents of ammonia of aquaculture effluents: a literature review / Uso de quitina y quitosana como adsorbentes de amonia de efluentes acuícolas: revisión de literatura

Os resíduos provenientes da aquicultura são derivados da ração e da excreção dos peixes e podem estar sedimentados, suspensos ou dissolvidos, ocasionando elevados valores de DBO, DQO, nitrogênio e fósforo. A produção de camarões no Brasil tem gerado elevadas quantidades de resíduos sólidos, tendo em vista que os exoesqueletos dos camarões correspondem a cerca de 40% do seu peso total, resultando num forte impacto ambiental. Diversas pesquisas envolvendo a quitina estão sendo desenvolvidas na área de tratamento de água, devido principalmente a sua capacidade de formar filme, sendo utilizada em sistemas filtrantes. Este polissacarídeo também pode ser utilizado como agente floculante no tratamento de efluentes, como adsorvente na clarificação de óleos, e principalmente na produção de quitosana. Atualmente a quitosana possui aplicações multidimensionais, desde áreas como a nutrição humana, biotecnologia, ciência dos materiais, indústria farmacêutica, agricultura, terapia genética e proteção ambiental. A quitosana é muito eficiente na remoção de poluentes em diferentes concentrações. Apresenta alta capacidade e grande velocidade de adsorção, boa eficiência e seletividade tanto em soluções que possuem altas ou baixas concentrações. O uso da biotecnologia, através do processo de adsorção utilizando adsorventes naturais e baratos, como a quitina e quitosana, minimiza os impactos ambientais da aquicultura tanto em relação aos provocados pelo lançamento de efluentes no meio ambiente quanto aos causados pelo descarte inadequado dos resíduos do processamento de camarões.(AU)

Aquaculture residues are derived from fish feed and excretion and may be sedimented, suspended or dissolved, resulting in high BOD, COD, nitrogen and phosphorus values. Shrimp production in Brazil has generated high amounts of solid waste, since shrimp exoskeletons account for about 40% of their total weight, resulting in a strong environmental impact. Several researches involving chitin are being developed in the area of water treatment, mainly due to its ability to form film, being used in filter systems. This polysaccharide can also be used as a flocculating agent in the treatment of effluents, as an adsorbent in the clarification of oils, and especially in the production of chitosan. Currently, chitosan has multidimensional applications, from areas such as human nutrition, biotechnology, materials science, pharmaceutical industry, agriculture, gene therapy and environmental protection. Chitosan is very efficient in the removal of pollutants at different concentrations. It presents high capacity and high adsorption velocity, good efficiency and selectivity both in solutions that have high or low concentrations. The use of biotechnology, through the adsorption process using natural and cheap adsorbents such as chitin and chitosan, minimizes the environmental impacts of aquaculture both in relation to those caused by the release of effluents into the environment and those caused by the inappropriate disposal of processing residues of shrimps.(AU)

Los residuos procedentes de la acuicultura se derivan de la ración y de la excreción de los peces y pueden estar sedimentados, suspendidos o disueltos, ocasionando elevados valores de DBO, DQO, nitrógeno y fósforo. La producción de camarones en Brasil ha generado grandes cantidades de residuos sólidos, teniendo en cuenta que los exoesqueletos de los camarones corresponden a cerca del 40% de su peso total, resultando en un fuerte impacto ambiental. Varias investigaciones involucrando la quitina se están desarrollando en el área de tratamiento de agua, debido principalmente a su capacidad de formar película, siendo utilizada en sistemas filtrantes. Este polisacárido también puede ser utilizado como agente floculante en el tratamiento de efluentes, como adsorbente en la clarificación de aceites, y principalmente en la producción de quitosana. Actualmente la quitosana posee aplicaciones multidimensionales, desde áreas como la nutrición humana, biotecnología, ciencia de los materiales, industria farmacéutica, agricultura, terapia genética y protección ambiental. La quitosana es muy eficiente en la eliminación de contaminantes en diferentes concentraciones. Presenta alta capacidad y gran velocidad de adsorción, buena eficiencia y selectividad tanto en soluciones que poseen altas o bajas concentraciones. El uso de la biotecnología, a través del proceso de adsorción utilizando adsorbentes naturales y baratos, como la quitina y quitosana, minimiza los impactos ambientales de la acuicultura tanto en relación a los provocados por el lanzamiento de efluentes en el medio ambiente en cuanto a los causados por el descarte inadecuado de los residuos del procesamiento de camarones.(AU)

Oxaliplatin delivery via chitosan/vitamin E conjugate micelles for improved efficacy and MDR-reversal in breast cancer.

A bioinspired chitosan/vitamin E conjugate (Ch/VES, 1:4) was synthesized, optimized based on chitosan's molecular weight (15, 300 kDa), and was assembled to entrap oxaliplatin (OXPt). 1H NMR, infrared spectroscopy, chromatography, X-ray photoelectron spectroscopy, X-ray diffraction, drug release, hemolysis, and stability studies were performed to characterize OXPt@Ch/VES micelles. The therapeutic efficacy of the micelles was tested in vitro in ER+/PR+/HER2- and triple-negative sensitive/resistant breast cancer cells, MCF-7 and MDA-MB-231 via cellular uptake, cytotoxicity, nuclear staining, DNA fragmentation, mitochondrial membrane potential, ROS generation, apoptosis, and cell cycle assays and in vivo using 4T1(Luc)-tumor-bearing mice. OXPt@Ch/VES Ms exhibited decreased IC50 towards MCF-7, MDA-MB-231 (sensitive/resistant) than OXPt. OXPt@Ch/VES Ms caused extensive DNA damage, mitochondrial depolarization, apoptosis, and cell-growth arrest (G2/M). OXPt@Ch/VES Ms treatment retarded tumor growth significantly, prolonged survival, and decreased nephrotoxicity than OXPt. The OXPt@Ch/VES Ms could serve as a potential nanomedicine to overcome conventional OXPt-mediated drug resistance/nephrotoxicity in breast cancer.

Novel chitosan-based nanocomposites as ecofriendly pesticide carriers: Synthesis, root rot inhibition and growth management of tomato plants.

Novel bio-based nanocomposites were developed as carriers for loading and sustained-release of vanillin (Van.) and cinnamaldehyde (Cinn.) antioxidants. The composites were obtained by intercalation of chitosan (CS) into sodium montmorillonite (CS/Mt), incorporation of chitosan with polyaniline (CS/PANI) and chitosan/polyaniline/exfoliated montmorillonite (CS/PANI/Mt). The structure and morphology of composites were characterized by FTIR, XRD, SEM and TEM. The release data of Van. and Cinn. from CS and CS/Mt obeyed well zero-order equation. However, Higuchi and Korsmeyer-Peppas models fitted well the release data from CS/PANI and CS/Mt composites. Their antifungal activity was examined towards Fusarium oxysporum and Pythium debaryanum. In vitro assay, CS, Cinn., Van., CS/PANI and CS/PANI/Cinn., have a strong inhibitory effect on the linear growth of the target pathogens, even at lower concentrations. Greenhouse assay indicated that seedling treatment by the loaded CS/PANI/Cinn and CS/Mt/Cinn. reduced both disease index and disease incidence parameters of both pathogens and possessed seedlings growth promoting potential of tomato compared to untreated-infected controls.

Chitosan derivatives functionalized dual ROS-responsive nanocarriers to enhance synergistic oxidation-chemotherapy.

The efficient triggering of prodrug release has become a challengeable task for stimuli-responsive nanomedicine utilized in cancer therapy due to the subtle differences between normal and tumor tissues and heterogeneity. In this work, a dual ROS-responsive nanocarriers with the ability to self-regulate the ROS level was constructed, which could gradually respond to the endogenous ROS to achieve effective, hierarchical and specific drug release in cancer cells. In brief, DOX was conjugated with MSNs via thioketal bonds and loaded with ß-Lapachone. TPP modified chitosan was then coated to fabricate nanocarriers for mitochondria-specific delivery. The resultant nanocarriers respond to the endogenous ROS and release Lap specifically in cancer cells. Subsequently, the released Lap self-regulated the ROS level, resulting in the specific DOX release and mitochondrial damage in situ, enhancing synergistic oxidation-chemotherapy. The tumor inhibition Ratio was achieved to 78.49%. The multi-functional platform provides a novel remote drug delivery system in vivo.

Injectable glycol chitosan thermogel formulation for efficient inner ear drug delivery.

We prepared a new injectable thermogel to enhance the efficiency of inner ear delivery of dexamethasone (DEX). Hexanoyl glycol chitosan (HGC) was synthesized and evaluated as an amphiphilic thermogel (Tgel ~ 32 °C) for use as a solubilizing agent as well as an injectable carrier for intratympanic delivery of the hydrophilic and hydrophobic forms of DEX. Various thermogel formulations with different drug types and concentrations were prepared, and their physicochemical and thermogelling properties were characterized by 1H NMR, ATR-FTIR, and rheometer. They exhibited versatile release kinetics from several hours to more than 2 weeks, depending on drug type and concentration. Our formulations further showed good residual stability for more than 21 days without any cytotoxicity or inflammation in the middle and inner ear and could deliver a considerably high drug concentration into the inner ear. Therefore, HGC thermogel has great potential as an effective and safe formulation for inner ear drug delivery.

Up-regulation of caveolin 1 mediated by chitosan activates Wnt/ ß-catenin pathway in chronic refractory wound diabetic rat model.

Diabetes mellitus (DM) can be implicated in the perturbations of vascular integrity and the dysfunction of angiogenesis. Chitosan has the advantage of promoting the vascular endothelial cell proliferation. However, the molecular mechanism of action in the promotion of wound healing by chitosan derivatives is still debated. In the current study, DM with chronic wound (CW) model rats were prepared and treated with chitosan. Vascular endothelial cells isolated from granulation tissues were conducted by RNA sequencing. Two thousand three hundred and sixteen genes were up-regulated, while 1,864 genes were down-regulated after chitosan treatment compared to CW group. Here, we observed that caveolin 1 (CAV1) was highly expressed induced by chitosan. Furthermore, we observed that CAV1 knockdown could compromise the activation of Wnt pathway by reduction of ß-catenin in rat aortic endothelial cells (RAOECs) and brain endothelium four cells (RBE4s). Moreover, we determined a direct interaction between CAV1 and ß-catenin by IP assay. The C-terminus of CAV1 and ß-catenin (24 to 586 amino acids) contributed to the interaction of these two proteins. Finally, the protein docking analysis indicated that the fragments of ß-catenin (253-261 'FYAITTLHN' and 292-303 'KFLAITTDCLQI') might have affected the structure by CAV1 and facilitated the resistance to degradation. Taken together, our study demonstrates that chitosan can up-regulate CAV1 expression, and CAV1 can interact with ß-catenin for promotion of canonical Wnt signaling pathway activity. Our results deepens the molecular mechanism of the Wnt pathway in vascular endothelial cells and is beneficial to developing new targets to assist in enhancing the pharmacological effect of chitosan on wound healing and angiogenesis against DM.

Rational formulation design of injectable thermosensitive chitosan-based hydrogels for cell encapsulation and delivery.

This work reports a rational design of injectable thermosensitive chitosan systems for cell encapsulation and delivery. Using mixtures of two phosphate salts, beta-glycerophosphate and ammonium hydrogen phosphate, we demonstrate that the pH and the osmolarity can be adjusted separately by varying the molar ratios between the salts and the d-glucosamine monomers. We found the existence of a critical temperature above which gelation time decays following a power-law. This gelation kinetics can be finely tuned through the pH and salt-glucosamine ratios. Formulations having physiological pH and osmolarity were produced for chitosan concentrations ranging from 0.4 to 0.9 wt%. They remain liquid for more than 2 h at 20 °C and form a macroporous gel within 2 min at 37 °C. In vitro encapsulation of pre-osteoblastic cells and gingival fibroblasts showed homogeneous cell distribution and good cell viability up to 24 h. Such an approach provides a valuable platform to design thermosensitive cell-laden systems.

Improvement in phenotype homeostasis of macrophages by chitosan nanoparticles and subsequent impacts on liver injury and tumor treatment.

When organic polymer-based drug nanocarriers become concentrated in macrophages, their influence on macrophage polarization has been rarely reported. This study prepared chitosan-based nanoparticles (CNs, 181.5 nm, +14.83 mV) and detected their impacts on macrophage reprogram. RT-PCR results showed in M1-like RAW264.7 cells (Mφ1), CNs decreased CD86 and iNOS expressions by 53.8% and 57.1%, and increased Arg-1 and IL-10 by 642.9% and 102.1%; in M2-like cells (Mφ2), CNs reduced Arg-1 and MR expressions by 70.7% and 93.0%, but increased CD86, iNOS and TNF-α by 290.4%, 86.2% and 728.6%; these results, consistent with cytokine secretions and surface CD86/CD206 expressions, showed CNs polarized Mφ1 and Mφ2 toward opposite type so as to improve the macrophage polarization homeostasis. In CCl4-induced mouse liver injury model, CNs reduced the hepatic Mφ1/Mφ2 ratio from 1.1 (model group) to 0.3, and then reduced the serum AST and ALT level by 42.3% and 39.0%; in mouse model of hepatocellular carcinoma, CNs decreased the number of CD163-positive cells and increased CD86-positive ones in tumor, and subsequently inhibited the tumor growth and metastasis. This study suggests CNs can improve the phenotype homeostasis of macrophages and subsequently promote the treatment of certain diseases such as liver injury and tumor.

Chitosan-based DDSs for pH/hypoxia dual-triggered DOX delivery: Facile morphology modulation for higher in vitro cytotoxicity.

The morphology of the drug delivery systems (DDSs) has been recognized to play an important role in their phagocytosis, cellular interaction and distribution. However, it is a technical challenge to simply prepare the non-spherical nanoscaled DDSs. Here, a facile strategy was developed to fabricate the pH/hypoxia dual-responsive nanowires by adding the maleic acid (MAH) and PEG modified chitosan (PEG-SS-CS-MAH) into aqueous solution of DOX. Compared with the PEG-SS-CS-MAH/DOX nanoparticles (NPs) by adding DOX into the PEG-SS-CS-MAH solution, the PEG-SS-CS-MAH/DOX nanowires (NWs) possessed a higher drug loading capacity of 58% and better pH/hypoxia dual-triggered DOX release performance with higher drug release in the simulated tumor intracellular microenvironment but a much lower premature drug leakage in the simulated normal physiological medium. As a result, higher in vitro anti-tumor efficacy was achieved with the PEG-SS-CS-MAH/DOX NWs, demonstrating their promising potential for tumor chemotherapy.

A dual-functional chitosan derivative platform for fungal keratitis.

Fungal keratitis remains a serious infectious ocular disease, and the traditional administration of eye drops is limited by ocular intrinsic barriers and drug shortages. Herein, we fabricated a chitosan-based dual-functional platform for ocular topical delivery of econazole. The platform can prolong the residence time on the ocular surface due to its strong interaction with the mucin layer by physical adhesion and covalent bonding, and also open corneal epithelial tight junctions for being positively charged, thereby enhancing corneal penetration of drug. Using these strategies, dosing concentration was reduced from 0.3 wt% to 0.1 wt%, dosing frequency was reduced from once-an-hour to twice-daily, in vitro and in vivo antifungal therapeutic effects were achieved and patient compliance could be improved. Given its high structural adaptability, many other ocular anterior segment-related diseases would benefit from this platform.

Efficacy and safety of a thermosensitive hydrogel for endoscopic submucosal dissection: An in vivo swine study.

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/ß-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 (mm2/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.

Potential Efficacy of Chitosan-Poly (Lactide-Co-Glycolide)-Encapsulated Trivalent Immersion Vaccine in Olive Flounder (Paralichthys olivaceus) Against Viral Hemorrhagic Septicemia Virus, Streptococcus parauberis Serotype I, and Miamiensis avidus (Scuticociliate).

Olive flounder (Paralichthys olivaceus) is the most valuable aquaculture species in Korea, corresponding to ~60% of its total production. However, infectious diseases often break out among farmed flounders, causing high mortality and substantial economic losses. Although some deleterious pathogens, such as Vibrio spp. and Streptococcus iniae, have been eradicated or contained over the years through vaccination and proper health management, the current disease status of Korean flounder shows that the viral hemorrhagic septicemia virus (VHSV), Streptococcus parauberis, and Miamiensis avidus are causing serious disease problem in recent years. Furthermore, these three pathogens have differing optimal temperature and can attack young fingerlings and mature fish throughout the year-round culture cycle. In this context, we developed a chitosan-poly(lactide-co-glycolide) (PLGA)-encapsulated trivalent vaccine containing formalin-killed VHSV, S. parauberis serotype-I, and M. avidus and administered it to olive flounder fingerlings by immersion route using a prime-boost strategy. At 35 days post-initial vaccination, three separate challenge experiments were conducted via intraperitoneal injection with the three targeted pathogens at their respective optimal temperature. The relative percentages of survival were 66.63%, 53.3%, and 66.75% in the group immunized against VHSV, S. parauberis serotype-I, and M. avidus, respectively, compared to the non-vaccinated challenge (NVC) control group. The immunized fish also demonstrated significantly (p < 0.05) higher specific antibody titers in serum and higher transcript levels of Ig genes in the mucosal and systemic tissues than those of NVC control fish. Furthermore, the study showed significant (p < 0.05) upregulation of various immune genes in the vaccinated fish, suggesting induction of strong protective immune response, ultimately leading to improved survival against the three pathogens. Thus, the formulated mucosal vaccine can be an effective prophylactic measure against VHS, streptococcosis, and scuticociliatosis diseases in olive flounder.

Antimicrobial and cytotoxic activity of electrosprayed chitosan nanoparticles against endodontic pathogens and Balb/c 3T3 fibroblast cells.

The aims of this study were to synthesize highly positively charged chitosan nanoparticles (Ch-Np) using the electrospraying technique, and to test their antimicrobial activity against endodontic pathogens, and cytotoxicity against fibroblast cells. Ch-Np were synthesized from low molecular weight chitosan (LMW-Ch) using the electrospraying technique, and characterized. The antimicrobial activity was evaluated against Streptococcus mutans, Enterococcus faecalis, and Candida albicans in their planktonic state using a Time-Kill Test performed by using broth micro-dilution technique, and against biofilm biomass using a microtiter plate biofilm assay. The cytotoxicity was evaluated using Balb/c 3T3 fibroblast cells with the standard MTT assay. Electrospraying of LMW-Ch produced Ch-Np with an average size of 200 nm, and a surface charge of 51.7 mV. Ch-Np completely eradicated S. mutans and E. faecalis in the planktonic state and showed fungistatic activity against C. albicans. Furthermore, it significantly reduced the biofilm biomass for all the tested microbial species [S. mutans (p = 0.006), E. faecalis (p < 0.0001), and C. albicans (p = 0.004)]. When tested for cytotoxicity using 3T3 cells, Ch-Np showed no cytotoxicity. In conclusion, the highly positively charged, colloidal dispersion of Ch-Np are effective as a biocompatible endodontic antimicrobial agent.

Dietary chitosan promotes the growth, biochemical composition, gut microbiota, hematological parameters and internal organ morphology of juvenile Barbonymus gonionotus.

In this study, we determined the effects of dietary chitosan on the growth, biochemical composition, gut microbiota, and hematological and histological parameters of juvenile Barbonymus gonionotus. Three test diets containing three different concentrations (1, 2, and 3 g kg-1 feed) of dietary chitosan were formulated. A basal diet without dietary chitosan was considered a control, and the fish were reared for 60 days. Comparing the effects of the dietary chitosan-containing diets with those of the control diet, we found that dietary chitosan significantly improved the muscle growth, nutrient and mineral contents, hematological parameters, lactic acid bacterium abundance, and digestive enzyme activities of B. gonionotus. Moreover, dietary chitosan significantly inhibited the growth of pathogenic bacteria in fish. Interestingly, an increase in the dietary chitosan level significantly enhanced the protein contents of the muscles and inversely significantly decreased the lipid contents compared to those with the basal diet. Quantitative study revealed that dietary chitosan significantly enhanced the length of intestinal villi, and qualitative study showed that dietary chitosan considerably reduced the fat content in the liver and improved the morphology of the kidney compared to those with the basal diet. Taken together, our results suggest that the application of dietary chitosan at a dose of 1 g kg-1 feed produced the highest benefit to treated B. gonionotus, indicating its potential for safe use in aquaculture.

Development and Evaluation of Thermosensitive Hydrogels with Binary Mixture of Scutellariae baicalensis radix Extract and Chitosan for Periodontal Diseases Treatment.

Scutellaria baicalensis root displays anti-inflammatory and antibacterial properties due to the presence of flavonoids, particularly baicalin, baicalein, and wogonin. Our work aimed at developing thermosensitive hydrogels containing a binary mixture of S. baicalensis radix lyophilized extract and chitosan as a novel approach for periodontal diseases treatment. Two types of chitosan were employed in preliminary studies on binary mixtures with S. baicalensis radix lyophilized extract standardized for baicalin, baicalein, and wogonin. Thermosensitive hydrogels were prepared of poloxamer 407, alginate sodium, and cellulose derivatives and evaluated in terms of rheological and mucoadhesive behavior. The presence of chitosan altered the release profile of active compounds but did not affect their in vitro permeation behavior in PAMPA assay. The synergistic effects of S. baicalensis radix lyophilized extract and chitosan toward ferrous ion-chelating activity, inhibition of hyaluronidase, and pathogen growth were observed. The thermosensitive gelling system showed shear-thinning properties, gelation temperature between 25 and 27 °C, and favorable mucoadhesiveness in contact with porcine buccal mucosa, which was enhanced in the presence of binary mixture of S. baicalensis radix extract and chitosan. The release tests showed that baicalin and baicalein were liberated in a prolonged manner with a fast onset from hydrogel formulations.

Non-clinical assessment of lubrication and free radical scavenging of an innovative non-animal carboxymethyl chitosan biomaterial for viscosupplementation: An in-vitro and ex-vivo study.

OBJECTIVE: Lubrication and free radical scavenging are key features of biomaterials used for viscosupplementation (VS) of joints affected by osteoarthritis (OA). The objective of this study was to describe the non-clinical performance characterization of KiOmedine® CM-Chitosan, a non-animal carboxymethyl chitosan, in order to assess its intended action in VS and to compare it to existing viscosupplements based on crosslinked hyaluronan (HA) formulations. METHOD: The lubrication capacity of the tested viscosupplements (VS) was evaluated in-vitro and ex-vivo. In-vitro, the coefficient of friction (COF) was measured using a novel tribological system. Meanwhile, an ex-vivo biomechanical model in ovine hindlimbs was developed to assess the recovery of join mobility after an intra-articular (IA) injection. Free radical scavenging capacity of HA and KiOmedine® CM-Chitosan formulations was evaluated using the Trolox Equivalent Antioxidant Capacity (TEAC) assay. RESULTS: In the in-vitro tribological model, KiOmedine® CM-Chitosan showed high lubrication capacity with a significant COF reduction than crosslinked HA formulations. In the ex-vivo model, the lubrication effect of KiOmedine® CM-Chitosan following an IA injection in the injured knee was proven again by a COF reduction. The recovery of joint motion was optimal with an IA injection of 3 ml of KiOmedine® CM-Chitosan, which was significantly better than the crosslinked HA formulation at the same volume. In the in-vitro TEAC assay, KiOmedine® CM-Chitosan showed a significantly higher free radical scavenging capacity than HA formulations. CONCLUSION: Overall, the results provide a first insight into the mechanism of action in terms of lubrication and free radical scavenging for the use of KiOmedine® CM-Chitosan as a VS treatment of OA. KiOmedine® CM-Chitosan demonstrated a higher capacity to scavenge free radicals, and it showed a higher recovery of mobility after a knee lesion than crosslinked HA formulations. This difference could be explained by the difference in chemical structure between KiOmedine® CM-Chitosan and HA and their formulations.

The Efficacy of Chitosan Hemostatic Pad on Hemostatic Function in Patients Undergoing Cardiac Catheterization: A Systematic Review and Meta-Analysis.

BACKGROUND: Chitin is a nitrogen-containing polysaccharide that can promote wound healing and stop bleeding. This paper investigates the effects of the addition of a chitin hemostatic patch on the time to arterial hemostasis, bleeding time, and reduction of the risk of bleeding and hematoma in patients undergoing cardiac catheterization. METHODS: Databases were searched for published clinical studies. The subjects were patients who received cardiac catheterization and had a chitin hemostatic patch added at the site of arterial puncture, while the control group received routine hemostatic treatment. The research quality was evaluated using the Cochrane risk-of-bias tool, version 2.0, and the meta-analysis was carried out using RevMan software. RESULTS: After searching literature databases, five randomized controlled trials were retrieved and included in the meta-analysis. The results showed that adding a chitin hemostatic patch could shorten the time to arterial hemostasis in patients, who received cardiac catheterization (Std. Mean Difference, -0.58; P < .001). In the subgroup analysis, the grouped effect of the chitin hemostatic patch on the bleeding time showed that the bleeding time was not significantly shortened after adding a chitin hemostatic patch in patients in the experimental group (RR, 0.78). At the same time, this measure did not significantly reduce the risk of arterial bleeding (RR, 0.49) or hematoma (RR, 0.73). CONCLUSIONS: The results of the meta-analysis showed that adding a chitin hemostatic patch at the site of arterial puncture in patients undergoing cardiac catheterization significantly reduced the time to hemostasis, but did not significantly reduce the incidence of bleeding and hematoma.