Optimization and evaluation of a chitosan-coated PLGA nanocarrier for mucosal delivery of Porphyromonas gingivalis antigens.

Recent advances in understanding Alzheimer's disease (AD) suggest the possibility of an infectious etiology, with Porphyromonas gingivalis emerging as a prime suspect in contributing to AD. P. gingivalis may invade systemic circulation via weakened oral/intestinal barriers and then cross the blood-brain barrier (BBB), reaching the brain and precipitating AD pathology. Based on the proposed links between P. gingivalis and AD, a prospective approach is the development of an oral nanovaccine containing P. gingivalis antigens for mucosal delivery. Targeting the gut-associated lymphoid tissue (GALT), the nanovaccine may elicit both mucosal and systemic immunity, thereby hampering P. gingivalis ability to breach the oral/intestinal barriers and the BBB, respectively. The present study describes the optimization, characterization, and in vitro evaluation of a candidate chitosan-coated poly(lactic-co-glycolic acid) (PLGA-CS) nanovaccine containing a P. gingivalis antigen extract. The nanocarrier was prepared using the double emulsion solvent evaporation method and optimized for selected experimental factors, e.g. PLGA amount, surfactant concentration, w1/o phase ratio, applying a d-optimal statistical design to target the desired physicochemical criteria for its intended application. After nanocarrier optimization, the nanovaccine was characterized in terms of particle size, polydispersity index (PdI), ζ-potential, encapsulation efficiency (EE), drug loading (DL), morphology, and in vitro release profile, as well as for mucoadhesivity, stability under simulated gastrointestinal conditions, antigen integrity, in vitro cytotoxicity and uptake using THP-1 macrophages. The candidate PLGA-CS nanovaccine demonstrated appropriate physicochemical, mucoadhesive, and antigen release properties for oral delivery, along with acceptable levels of EE (55.3 ± 3.5 %) and DL (1.84 ± 0.12 %). The integrity of the encapsulated antigens remained uncompromised throughout NPs production and simulated gastrointestinal exposure, as confirmed by SDS-PAGE and Western blotting analyses. Furthermore, the nanovaccine showed effective in vitro uptake, while exhibiting low cytotoxicity. Taken together, these findings underscore the potential of PLGA-CS NPs as carriers for adequate antigen mucosal delivery, paving the way for further investigations into their applicability as vaccine candidates against P. gingivalis.

Effect of feeding chitosan and blend of essential organic acids on growth performance, haematological parameters and innate immunity in early aged male layer chicks.

The use of antibiotics as conventional feed additives in poultry operations have proven useful, however resulted serious health concerns to consumer due to their bio-accumulation, besides rising problem of antimicrobial resistance in microbes, thus, an alternative to antibiotic growth promoter have called for. One of the aim of the experiment was to assess the lone and combined effects of feeding of chitosan oligosaccharide (COS) and blend of organic acids and short chain fatty acids in essential oils on growth performance, haematological parameters, relative lymphoid organ weight and innate immunity in early aged layer chick (male birds). A total of ninety, day-old chicks were randomly allotted into five groups: CO, Control group fed only poultry feed ; AGP, antibiotic growth promoter fed Avilomycin at the dose of 200 mg/kg of poultry feed; CH, chitosan oligosaccharide fed at the rate of 100 mg/kg feed; OE, blend of organic acids and short chain fatty acids in essential oils contained 1000 to 2000 mg/kg feed in a graded dose per week and CH + OE, chitosan oligosaccharide plus blend of organic acids and short chain fatty acids in essential oils at consistent rate and manner as followed for each of given feed additives when fed individually. Data on growth performance, samples for haematological parameters and innate immunity were measured and assayed on 7th, 21st and 42nd day post feeding (dpf) respectively. The results showed that compared with the control group; there is a marginal gain in body weight at 7th and 21st dpf in CH group and the corresponding CH + OE group. Feed conversion ratio in CH group was remarkably good at 7th and 21st dpf. No significant difference was observed in relative organ weights of thymus, spleen and Bursa of Fabricius in treatment groups as compared to control birds; however a significant rise in splenic weight index in OE fed birds at 42nd dpf noted. Haematological changes were inconsequential in treatment groups with an exception to enhancement of heterophil to lymphocyte ratio (H:L ratio) in CH group at 42nd dpf. Serum lysozyme activity proportionately elevated in CH + OE group on 21st and 42nd dpf when measured against control group; on the other hand no detectable augmentation of gut lysozyme activity observed. Both serum bactericidal and gut bactericidal activity boosted in combinatorial group at 42nd dpf. These results indicated that early age feeding of chitosan individually or combination with organic acids and short chain fatty acids in layer chick is beneficial, as it has the potential to enhance body weight gain to some extent and improves systemic and localized innate immunity to offer protection against infectious assaults thus may avoid early chick mortality in farms.

Chitosan-coated PLGA microemulsion loaded with tannic acid against Escherichia coli in vitro and in vivo.

The overuse of antibiotics has resulted in a surge of drug-resistant bacteria, making the pursuit of natural antimicrobials an urgent and significant trend. Encapsulation and nanoparticulation are effective ways to enhance the antibacterial properties of natural drugs. In this study, we encapsulated tannic acid (TA) with chitosan (CS) and poly (lactide-co-glycolide) (PLGA) using the emulsion-solvent evaporation method to enhance the antimicrobial effect of TA. We prepared a bilayer membrane spherical nanoemulsion of TA-PLGA-CS (TPC) with uniform size of 559.87 ± 1.16 nm, and zeta potential of 59.53 ± 1.07 mV. TPC could be stably stored for 90 days at 4°C without affecting the properties of the emulsion, and the minimum bactericidal concentration against four strains of Escherichia coli (E. coli) remained unchanged for 60 d. The results indicated that TPC enhanced the inhibitory effect of TA against E. coli. Scanning electron microscope images revealed that TPC treatment caused damage to the bacterial cell membrane. In addition, in vivo experiments indicated that TPC exhibited a superior therapeutic effect on artificial colibacillosis in chickens infested with Avian pathogenic Escherichia coli, as evidenced by the changes in body weight and a reduction bacterial load in heart. Furthermore, TPC reversed the down-regulation of catalase, glutathione peroxidase1 (GPX1), and GPX7 gene expression levels in intestinal tissues. Compared to the model group, TPC treatment elevated serum glutathione peroxidase activities and lowered myeloperoxidase and lactate dehydrogenase levels, offering antioxidant protection that was slightly better than that of doxycycline hydrochlorid group. In summary, we prepared a novel TA antimicrobial preparation with significant antioxidant potential and inhibitory effect against E. coli both in vitro and in vivo.

An oil-in-gel type of organohydrogel loaded with methylprednisolone for the treatment of secondary injuries following spinal cord traumas.

The secondary injuries following traumatic spinal cord injury (SCI) is a multiphasic and complex process that is difficult to treat. Although methylprednisolone (MP) is the only available pharmacological regime for SCI treatment, its efficacy remains controversial due to its very narrow therapeutic time window and safety concerns associated with high dosage. In this study, we have developed an oil-in-gel type of organohydrogel (OHG) in which the binary oleic-water phases coexist, for the local delivery of MP. This new OHG is fabricated by a glycol chitosan/oxidized hyaluronic acid hydrophilic network that is uniformly embedded with a biocompatible oil phase, and it can be effectively loaded with MP or other hydrophobic compounds. In addition to spatiotemporally control MP release, this biodegradable OHG also provides a brain tissue-mimicking scaffold that can promote tissue regeneration. OHG remarkably decreases the therapeutic dose of MP in animals and extends its treatment course over 21 d, thereby timely manipulating microglia/macrophages and their associated with signaling molecules to restore immune homeostasis, leading to a long-term functional improvement in a complete transection SCI rat model. Thus, this OHG represents a new type of gel for clinical treatment of secondary injuries in SCI.

Immunization with the glutathione S-transferase Sj26GST with Chi-CpG NP against Schistosoma japonicum in mice.

Schistosomiasis caused by Schistosoma japonicum (S. japonicum) is a major public health problem in the Philippines, China and Indonesia. In this study, the immunopotentiator CpG-ODN was encapsulated within chitosan nanoparticles (Chi NPs) to create a combination adjuvant (Chi-CpG NP). This approach was employed to enhance the immunogenicity of 26 kDa glutathione S-transferase (Sj26GST) from S. japonicum through intranasal immunization. The results demonstrated higher levels of specific anti-Sj26GST antibodies and Sj26GST-specific splenocyte proliferation compared to mice that were immunized with Sj26GST + Chi-CpG NP. Cytokine analysis of splenocytes revealed that the Sj26GST + Chi-CpG NP induced a slight Th1-biased immune response, with increased production of IFN-γ by CD4+ T-cells in the spleen. Subsequently, mice were intradermally inoculated with 1 × 107 organisms in the Coeliac cavity. The bacterial organ burden detected in the liver of immunized mice suggested that Sj26GST + Chi-CpG NP enhances protective immunity to inhibit S. japonicum colonization. Therefore, Sj26GST + Chi-CpG NP vaccination enhances Sj26GST-specific immunogenicity and provides protection against S. japonicum.

Enhancing linezolid activity in the treatment of oral biofilms using novel chitosan microneedles with iontophoretic control.

This study aimed to prepare and assess active microneedle (MN) patches based on a novel biomaterial and their effective coupled (physical and electrical) transdermal delivery of a model drug (Linezoid). Modified MN patches (e.g. fabricated from Linezoid, boronated chitosan, polyvinyl alcohol and D-sorbitol) were engineered using a vacuum micromoulding method. Physicochemical, FTIR (Fourier transform infrared), in-silico, structural and thermal analysis of prepared formulations were conducted to ascertain MN quality, composition and integrity. In-vitro mechanical tests, membrane toxicity, drug release, antibiofilm, ex-vivo mucoadhesion, insertion and in-vivo antibiofilm studies were performed to further validate viability of the coupled system. Optimized MN patch formulation (CSHP3 - comprising of 3 % w/v boronated chitosan, 3.5 % w/v PVA and 10 % w/w D-sorbitol) exhibited sharp-tipped, equi-distant and uniform-surfaced micron-scaled projections with conforming physicochemical features. FTIR analysis confirmed modification (i.e., boronation) of chitosan and compatibility as well as interaction between CSHP3 constituents. In-silico analysis indicated non-covalent interactions between all formulation constituents. Moreover, boronated chitosan-mucin glycoprotein complex showed a stronger bonding (∼1.86 times higher CScore) as compared to linezolid-mucin counterpart. Thermal analysis indicated amorphous nature of CSHP3. A âˆ¼ 1.42 times higher tensile strength was displayed by CSHP3 as compared to control (i.e., pure chitosan, polyvinyl alcohol and D-sorbitol-based MN patch). Membrane toxicity study indicated non-toxic and physiological compatible nature of CSHP3. Within 90 min, 91.99 ± 2.3 % linezolid was released from CSHP3. During release study on agarose gel, CSHP3-iontophoresis treatment resulted in a âˆ¼ 1.78 and âˆ¼ 1.20 times higher methylene blue-covered area and optical density, respectively, within 60 min as compared to CSHP3 treatment alone. Staphylococcus aureus biofilms treated with CSHP3 exhibited 65 ± 4.2 % reduction in their mass. CSHP3 MN patches remained adhered to the rabbit oral mucosa for 6 ± 0.15 h. Mucosa treated with CSHP3 and CSHP3-iontophoresis combination showed a generation of pathways in the epithelium layers without any damage to the underlying lamina propria. Eradication of Staphylococcus aureus from oral mucosal wounds and complete tissue regeneration was recorded following 7-day treatment using CSHP3-iontophoresis coupled approach.

Effective cerebral tuberculosis treatment via nose-to-brain transport of anti-TB drugs using mucoadhesive nano-aggregates.

Central nervous system tuberculosis (CNS-TB) is a severe form of extra-pulmonary tuberculosis with high mortality and morbidity rates. The standard treatment regimen for CNS-TB parallels that of pulmonary TB, despite the challenge posed by the blood-brain barrier (BBB), which limits the efficacy of first-line anti-TB drugs (ATDs). Nose-to-brain (N2B) drug delivery offers a promising solution for achieving high ATD concentrations directly at infection sites in the brain while bypassing the BBB. This study aimed to develop chitosan nanoparticles encapsulating ATDs, specifically isoniazid (INH) and rifampicin (RIF). These nanoparticles were further processed into micro-sized chitosan nano-aggregates (NA) via spray drying. Both INH-NA and RIF-NA showed strong mucoadhesion and significantly higher permeation rates across RPMI 2650 cells compared to free ATDs. Intranasal administration of these NAs to TB-infected mice for four weeks resulted in a significant reduction of mycobacterial load by approximately ∼2.86 Log 10 CFU compared to the untreated group. This preclinical data highlights the efficacy of intranasal chitosan nano-aggregates in treating CNS-TB, demonstrating high therapeutic potential, and addressing brain inflammation challenges. To our knowledge, this study is the first to show nasal delivery of ATD nano-formulations for CNS-TB management.

Corticosteroid-loaded chitosan-based in-situ forming gel combined with microneedle technology for improvement of burn eschar wound healing.

Burn is one of the most common skin injuries and accounts for 300,000 deaths annually. Debridement and antibiotic therapy are major burn treatments, however, as debridement is not always possible and many drugs have poor penetration into necrotic tissue, permeation enhancement is acquired. Another challenge is the short duration of topically applied drugs. This study aims to address both problems by combining in-situ forming gels and microneedles. A chitosan-based in-situ forming gel of hydrocortisone was applied to human burn eschar using microneedles. The formulation was optimized using Design-Expert software. Formulation characterization was done in terms of gelling time and temperature, thermal analysis, release phenomenon, rheology, texture analysis, and stability. Finally, animal studies on mice burn wound treatment were conducted. Results showed that optimized formulation controlled the drug release, and wherever microneedle was used, drug permeation and flux increased (P-value < 0.05). In all ex-vivo and in-vivo stages, gel plus microneedle (length of 1.5 mm and application mode of 2) produced the best results concerning increased flux and faster recovery of burn eschar. In conclusion, the in-situ forming gel with appropriate texture, quality, and stability in combination with microneedle can be a good candidate for the controlled release of drugs in third-degree burn eschars.

(S)-3-(3,4-Dihydroxybenzyl) piperazine-2,5-dione (cyclo-Gly-L-DOPA or CG-Nio-CGLD) peptide loaded in Chitosan Glutamate-Coated Niosomes as anti-Colorectal cancer activity.

BACKGROUND: Colorectal cancer (CRC), now the second most prevalent malignant tumor worldwide, is more prevalent in young adults. In recent decades, there has been progress in creating anti-colorectal cancer medications, including cytotoxic compounds. OBJECTIVES: Novel anticancer drugs are needed to surmount existing obstacles. A recent study investigated the effectiveness of novel formulations in preventing colorectal cancer. METHODS: During this study, we assessed a new kind of niosome called cyclo-Gly-L-DOPA (CG-Nio-CGLD) made from chitosan glutamate. We evaluated the anti-colorectal cancer properties of CG-Nio-CGLD utilizing CCK-8, invasion assay, MTT assay, flow cytometry, and cell cycle analysis. The transcription of genes associated with apoptosis was analyzed using quantitative real-time PCR. At the same time, the cytotoxicity of nanomaterials on both cancer and normal cell lines was assessed using MTT assays. Novel anticancer drugs are needed to surmount existing obstacles. A recent study investigated the effectiveness of newly developed formulations in preventing colorectal cancer. RESULTS: The Nio-CGLD and CG-Nio-CGLD were spherical mean diameters of 169.12 ± 1.87 and 179.26 ± 2.17 nm, respectively. Entrapment efficiency (EE%) measurements of the Nio-CGLD and CG-Nio-CGLD were 63.12 ± 0.51 and 76.43 ± 0.34%, respectively. In the CG-Nio-CGLD group, the percentages of early, late, necrotic, and viable CL40 cells were 341.93%, 23.27%, 9.32%, and 25.48%. The transcription of the genes PP53, cas3, and cas8 was noticeably higher in the treatment group compared to the control group (P > 0.001). Additionally, the treatment group had lower BCL2 and survivin gene expression levels than the control group (P < 0.01). Additionally, CG-Nio-CGLD formulations demonstrated a biocompatible nanoscale delivery mechanism and displayed little cytotoxicity toward the CCD 841 CoN reference cell line. CONCLUSION: These findings indicate that chitosan-based noisome encapsulation may enhance the effectiveness of CG-Nio-CGLD formulations in fighting cancer.

Effects of dietary Chitosan oligosaccharides supplementation on Th17/Treg balance and gut microbiota of early weaned pigeon squabs.

Our previous study found that early weaning is associated with decreased growth performance, intestinal barrier impairment, and an imbalance in Th17/Treg in pigeon squabs. Chitosan oligosaccharides (COS) has been substantiated to regulate gut microbiota and restore Th17/Treg equilibrium in mammals, thereby ameliorating growth performance. However, the potential effects of COS in altricial birds remain unclear. Three hundred healthy 7-day-old American king pigeon squabs were selected with similar body weights and randomly divided into 5 groups. The 5 treatment groups were as follows: the control group (CON), fed with artificial pigeon milk; 4 supplementation groups, fed with artificial pigeon milk +100 (COS1), 150 (COS2), 200 (COS3), and 250 (COS4) mg/kg COS, respectively. Results showed that dietary supplementation of COS significantly enhanced the growth performance of weaned squabs. Compared to the CON group, the COS groups exhibited increased villus length and villus area in the jejunum and ileum, accompanied by improvements in morphological structure and mucosal permeability. COS was found to reduce the levels of Th17-associated cytokines and increase the levels of Treg-associated cytokines. COS downregulated the expression of retinoic acid receptor-related orphan receptor C (RORC), a key transcription factor of Th17 cells, while upregulated the expression of Forkhead box protein P3 (FOXP3), a key transcription factor of Treg cells. Dietary COS supplementation increased gut bacterial diversity, altered the relative abundance of several bacteria taxa and enhanced the concentration of short-chain fatty acids (SCFA). Correlation analysis demonstrated a close association between gut microbiota, SCFAs, and indicators related to the Th17/Treg balance. Moreover, we found that SCFAs correlated more strongly with Th17/Treg-related indexes than gut microbiota. These results demonstrated that COS could relieve early weaning stress in pigeon squabs and the optimal dosage of dietary COS supplementation was suggested to be 200 mg/kg. In addition, COS had a protective effect on maintaining intestinal immune balance by modulating microbiota and Th17/Treg related signaling pathways, in which SCFAs might play a crucial role as messengers.

Chitosan and liposomal delivery systems for epicatechin or propyl gallate targeting localized treatment of vulvovaginal candidiasis.

Natural polyphenols are promising alternatives to antifungals for novel treatments of vulvovaginal candidiasis (VVC) in an era of antimicrobial resistance. However, polyphenols are poorly soluble and prone to degradation. To overcome their limitations, we propose incorporation in liposomes. The study aimed to develop chitosan and liposome comprising delivery systems for epicatechin (EC) or propyl gallate (PG) as treatment of VVC. EC was selected for its antioxidative properties and PG as an ester of antifungal gallic acid. To improve formulation retention at vaginal site, mucoadhesive chitosan was introduced into formulation as liposomal surface coating or hydrogel due to intrinsic antifungal properties. These polyphenol-loaded liposomes exhibited an average size of 125 nm with a 64 % entrapment efficiency (for both polyphenols). A sustained in vitro polyphenol release was seen from liposomes, particularly in chitosan hydrogel (p < 0.01 or lower). Viscosity was evaluated since increased viscosity upon mucin contact indicated adhesive bond formation between chitosan and mucin confirming mucoadhesiveness of formulations. Antifungal activity was evaluated by the broth microdilution method on Candida albicans CRM-10231. Unlike PG, incorporation of EC in liposomes enabled antifungal activity. Fungicidal activity of chitosan was confirmed both when used as liposomal coating material and as hydrogel vehicle.

Florfenicol core-shell composite nanogels as oral administration for efficient treatment of bacterial enteritis.

To reduce the bitterness of florfenicol, avoid its degradation by gastric acid, and enhance its antibacterial activity against Escherichia coli by targeting and slowly releasing drugs at the site of intestinal infection, with pectin as an anion carrier and chitosan oligosaccharides (COS) as a cationic carrier, florfenicol-loaded COS@pectin core nanogels were self-assembled by electrostatic interaction and then encapsulated in sodium carboxymethylcellulose (CMCNa) shell nanogels through the complexation of CMCNa and Ca2+ to prepare florfenicol core-shell composite nanogels in this study. The florfenicol core-shell composite nanogels were investigated for their formula choice, physicochemical characterization, pH-responsive performances, antibacterial activity, therapeutic efficacy, and in vitro and in vivo biosafety studies. The results indicated that the optimized formula was 0.6 g florfenicol, 0.79 g CMCNa, 0.30 g CaCl2, 0.05 g COS, and 0.10 g pectin, respectively. In addition, the mean particle diameter, polydispersity index, zeta potential, loading capacity, and encapsulation efficiency were 124.0 ± 7.2 nm, -22.9 ± 2.5 mV, 0.42 ± 0.03, 43.4 % ± 3.1 %, and 80.5 % ± 3.4 %, respectively. The appearance, lyophilized mass, resolvability, scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), and fourier transform infrared (FTIR) showed that the florfenicol core-shell composite nanogels were successfully prepared. Florfenicol core-shell composite nanogels had satisfactory stability, rheology, and pH-responsiveness, which were conducive to avoid degradation by gastric acid and achieve targeted and slow release at intestinal infection sites. More importantly, florfenicol core-shell composite nanogels had excellent antibacterial activity against Escherichia coli, a satisfactory therapeutic effect, and good palatability. In vitro and in vivo biosafety studies suggested the great promise of florfenicol core-shell composite nanogels. Therefore, the prepared florfenicol core-shell composite nanogels may be helpful for the treatment of bacterial enteritis as a biocompatible oral administration.

Encapsulation of Citrus sinensis essential oil and R-limonene in lipid nanocarriers: A potential strategy for the treatment of leishmaniasis.

Leishmaniases, a group of neglected tropical diseases caused by an intracellular parasite of the genus Leishmania, have significant impacts on global health. Current treatment options are limited due to drug resistance, toxicity, and high cost. This study aimed to develop nanostructured lipid carriers (NLCs) for delivering Citrus sinensis essential oil (CSEO) and its main constituent, R-limonene, against leishmaniasis. The influence of surface-modified NLCs using chitosan was also examined. The NLCs were prepared using a warm microemulsion method, and surface modification with chitosan was achieved through electrostatic interaction. These nanocarriers were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), transmission electron microscopy, and dynamic light scattering (DLS). In vitro cytotoxicity was assessed in L929 and RAW 264.7 cells, and leishmanicidal activity was evaluated against promastigote and amastigote forms. The NLCs were spherical, with particle sizes ranging from 97.9 nm to 111.3 nm. Chitosan-coated NLCs had a positive surface charge, with zeta potential values ranging from 45.8 mV to 59.0 mV. Exposure of L929 cells to NLCs resulted in over 70 % cell viability. Conversely, surface modification significantly reduced the viability of promastigotes (93 %) compared to free compounds. Moreover, chitosan-coated NLCs presented a better IC50 against the amastigote forms than uncoated NLCs. Taken together, these findings demonstrate the feasibility of using NLCs to overcome the limitations of current leishmaniasis treatments, warranting further research.

Course-based intra-articular injection of medical chitosan mitigates excessive deposition of triacylglycerides in the synovial tissue of the knee osteoarthritis.

BACKGROUND: This study aimed to investigate the clinical efficacy of intra-articular injections of medical chitosan for treating knee osteoarthritis (KOA) and measure the lipid metabolism profiles of the synovial tissue. METHODS: Sixty patients with KOA undergoing conservative treatment were recruited and randomized into two groups: one without pharmacological intervention (OA group) and the other receiving course-based intra-articular medical chitosan injections (CSI group). Quantitative lipidomic profile of synovial tissue was analyzed. Functional scores, including Kellgren-Lawrence rating (K-L), Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scoring, and American Knee Society (AKS) scoring were conducted. RESULTS: Survival from the initial conservative treatment to final knee arthroplasty was significantly longer in the CSI group compared to the OA group. Except for the presurgery VAS score, no statistically significant differences were observed in the other scores, including K-L, initial VAS, WOMAC, and AKS. However, the CSI group experienced more reductions in AKS-Knee subscores compared to the OA group. Compared to the CSI group, the OA group exhibited a significant upregulation in most differential lipids, particularly triacylglycerides (TAGs, 77%). The OA group had notably higher levels of long-chain unsaturated fatty acids. CONCLUSION: Intra-articular injection of medical chitosan significantly prolongs the survival period before knee arthroplasty and reduces the deposition of TAGs metabolites.

Nitroxide radical conjugated ovalbumin theranostic nanosystem for enhanced dendritic cell-based immunotherapy and T1 magnetic resonance imaging.

Melanoma, known for its aggressive metastatic nature, presents a formidable challenge in cancer treatment, where conventional therapies often fall short. This study introduces a pioneering approach utilizing metal-free nanosystem as tumor vaccines, spotlighting their potential in revolutionizing melanoma treatment. This work employed organic nitroxides, specifically 4-carboxy-TEMPO, in combination with chitosan (CS), to create a novel nanocomposite material - the CS-TEMPO-OVA nanovaccines. This composition not only improves biocompatibility and extends blood circulation time of TEMPO but also marks a significant departure from traditional gadolinium-based contrast agents in MRI technology, addressing safety concerns. CS-TEMPO-OVA nanovaccines demonstrate excellent biocompatibility at both the cellular and organoid level. They effectively stimulate bone marrow-derived dendritic cells (BMDCs), which in turn promote the maturation and activation of T cells. This ultimately leads to a strong production of essential cytokines. These nanovaccines serve a dual purpose as both therapeutic and preventive. By inducing an immune response, activating cytotoxic T cells, and promoting macrophage M1 polarization, they effectively inhibit melanoma growth and enhance survival in mouse models. When combined with αPD-1, the CS-TEMPO-OVA nanovaccines significantly bolster the infiltration of cytotoxic T lymphocytes (CTLs) within tumors, sparking a powerful systemic antitumor response that effectively curbs tumor metastasis. The ability of these nanovaccines to control both primary (subcutaneous) and metastatic B16-OVA tumors highlights their remarkable efficacy. Furthermore, the CS-TEMPO-OVA nanovaccine can be administered in vivo via both intravenous and intramuscular routes, both of which effectively enhance the T1 contrast of magnetic resonance imaging in tumor tissue. This study offers invaluable insights into the integrated application of these nanovaccines in both clinical diagnostics and treatment, marking a significant stride in cancer research and patient care.

A blend of chitosan-vitamin C and vitamin E nanoparticles robust the immunosuppressed- status in Nile tilapia treated with salt.

In aquaculture, fish are exposed to many stressors, such as climate changes and infectious diseases that affect their performance, immunity, and welfare. Freshwater fish subjected to salt bath become exhausted and stressed. In this experiment, Nile tilapia were exposed to a salt bath at a dose of 30 ppt for 30 min a day. Vitamin C and vitamin E are well-known antioxidants that are used in aquaculture. Fish received dietary nanoparticles of chitosan-vitamin C and chitosan-vitamin E (CCE-NPs) for different periods (7 and 14 days) pre- (G2) and post-salt treatment (G3). In the control fish (G1), cortisol 5.44 µg/dL and glucose 91.67 mg/dL were significantly up-regulated post-salt treatment by 1 h and 24 h, respectively, whereas those (G2) fed CCE-NPs diet had significantly lower values of 4.72 and 3.25 µg/dL; 86.3 and 84.3 mg/dL, respectively. A rapid decrease of glucose 68.3 and 66.3 mg/dL was noticed in those (G2) fed CCE-NPs diet compared to the control 84.67 mg/dL at 48 h post-stress. Regardless of the supplementation period, fish (G2) could partially restore normal food reflex at 48 h (post-salt bath) and fully restored at 72 h compared to 7 days in the control (G1). After 48 h, fish that received dietary CCE-NPs (G2 and G3) restored normal mucus lysozyme levels, whereas the control did not restore pre-treatment values till the seventh day. Mucus antibacterial activity, fish received rapid dietary CCE-NPs (G2) and partially restored average values (pre-salt bath) at 96 h. The salt treatment could provoke gene expression of pro-inflammatory cytokines interleukin (IL-1ß) and tumor necrosis (TNF)-α in the head kidney of fish at 24 h post-salt bath to 5.9-8.35 fold-change, respectively, with a rapid decline in fish (G2) the gene expression. Post-salt bath (24 h), the gene expression of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) was higher in fish (G2) than in the control group (G1) regardless of the supplementation period (7 and 14 days). Bacterial infection S. agalactiae (OL471408), a significantly lower MR was recorded in G2 at 40% and 33.3% compared to the control G1 MR (53.3%), with an RPL of 24.95% and 37.5%. In conclusion, Nile tilapia treated with a 30 ppt salt became more vulnerable to S. agalactiae. Adding CCE-NPs to the Nile tilapia diet for 7- and 14-day pre-salt bath could increase immune and antioxidant-related gene expression to counteract S. agalactiae infection.

Oral administration of encapsulated catechin in chitosan-alginate nanoparticles improves cognitive function and neurodegeneration in an aluminum chloride-induced rat model of Alzheimer's disease.

The present study aimed to investigate the effect of catechin-loaded Chitosan-Alginate nanoparticles (NPs) on cognitive function in an aluminum chloride (AlCl3)-induced rat model of Alzheimer's disease (AD). The Catechin-loaded Chitosan-Alginate nanocarriers were synthesized through ionotropic gelation (IG) method. Physio-chemical characterization was conducted with the Zetasizer Nano system, the scanning electron microscope, and the Fourier transform infrared spectroscopy. The experiments were performed over 21 days on six groups of male Wistar rats. The control group, AlCl3 treated group, Catechin group, nanocarrier group, treatment group 1 (AlCl3 + Catechin), and treatment group 2 (AlCl3 + nanocarrier). A behavioral study was done by the Morris water maze (MWM) test. In addition, the level of oxidative indices and acetylcholine esterase (AChE) activity was determined by standard procedures at the end of the study. AlCl3 induced a significant increase in AChE activity, along with a significant decrease in the level of Catalase (CAT) and total antioxidant capacity (TAC) in the hippocampus. Moreover, the significant effect of AlCl3 was observed on the behavioral parameters of the MWM test. Both forms of Catechin markedly improved AChE activity, oxidative biomarkers, spatial memory, and learning. The present study indicated that the administration of Catechin-loaded Chitosan-Alginate NPs is a beneficial therapeutic option against behavioral and chemical alteration of AD in male Wistar rats.

Exploring the effects of varying levels of selenium-chitosan on production performance, egg quality, and immune health in laying japanese quail.

The purpose of this research was to see how different levels of Se-chitosan, a novel organic source of Se, affected the production performance, egg quality, egg Se concentration, microbial population, immunological response, antioxidant status, and yolk fatty acid profile of laying Japanese quail. This experiment used a totally randomized design, with 5 treatments, 6 repeats, and 10 birds in each repetition. The dietary treatment groups were as follows: no Se supplementation (control group), 0.2 mg/kg Na-selenite supplementation, and 0.2, 0.4, and 0.6 mg/kg Se-chitosan supplementation. The feed conversion ratio (FCR) improved linearly in quails fed different levels of Se-chitosan compared to the control group (P < 0.05). Furthermore, Se-chitosan at concentrations of 0.2 and 0.4 mg/kg demonstrated both linear and quadratic increases in albumen height, Haugh unit, and yolk color in fresh eggs compared to the control group. Additionally, Se-chitosan contributed to enhanced shell thickness and strength, along with an increased Se concentration in the yolk. Se-chitosan supplementation at different levels linearly and quadratically reduced coliforms (COL) while increasing lactic acid bacteria (LAB)/coliform ratios (P < 0.05). Se-chitosan supplementation linearly and quadratically increased the total antibody response to sheep red blood cells (SRBC) and IgG titers (P < 0.05). It also linearly decreased the level of malondialdehyde in fresh and stored egg yolks and increased the activity of antioxidant enzymes catalase and glutathione peroxidase linearly, and superoxide dismutase (SOD) both linearly and quadratically in quail blood serum (P < 0.05). Additionally, supplementation of Se-chitosan at levels of 0.2 and 0.6 mg/kg linearly decreased the ∑ n-6 PUFA/∑ n-3 PUFA ratio in the yolk compared to the control group (P < 0.05). It can be concluded that incorporating Se-chitosan as a novel organic source of Se in the diet of laying quails can enhance production performance, egg quality, egg Se concentration, yolk lipid oxidation, microbial population, immune response, antioxidant enzyme activity, and yolk fatty acid profile.

Efficacy Analysis of Arthroscopic Surgery Combined with Intra-articular Chitosan Injection for Stage II-III Knee Osteoarthritis in Patients with Abnormal Body Weight.

OBJECTIVE: Weight is an influential factor in knee osteoarthritis (KOA). However, the effect of abnormal body weight on chitosan's efficacy in treating KOA is unclear. This study aimed to explore the differences in the effectiveness of arthroscopic surgery combined with intra-articular chitosan injection for KOA in patients with abnormal body weight. METHODS: Patients with stage II-III KOA (Kellgren-Lawrence rating, K-L) undergoing arthroscopic surgery were recruited for this clinical study from January 2020 to September 2021. Based on body mass index (BMI) and intra-articular chitosan injection, patients with KOA undergoing arthroscopic surgery (138 patients) were divided into four groups: low-weight-non-injection (Lw-N, BMI <18.5); low-weight-chitosan injection (Lw-CS, BMI <18.5); overweight-non-injection (Ow-N, BMI ≥25); overweight-chitosan injection (Ow-CS, BMI ≥25). A 2-year follow-up was conducted to evaluate various indicators, including the visual analogue scale (VAS) and the Western Ontario and McMaster Universities osteoarthritis index score (WOMAC). Statistical analyses were performed using relevant parametric or non-parametric tests. RESULTS: In total, 138 patients with KOA were included in this study. There were no significant differences in gender, age, and incidence of chronic residual pain after arthroscopy among the four groups (p > 0.05). The proportion of patients undergoing subsequent knee arthroplasty during the 2-year follow-up period was significantly higher in the Ow-CS group (20/35) than in the Lw-CS group (12/39) (p < 0.05). The K-L rating showed an overall increasing trend over time, with the K-L rating in the Ow-N and Ow-CS groups significantly higher than that in the Lw-CS group at the final follow-up (p < 0.05). VAS and WOMAC scores significantly decreased at 1 and 3 months post-arthroscopy and then increased. One month after arthroscopy, VAS was significantly lower (p < 0.05) in the intra-articular chitosan injection groups (Lw-CS and Ow-CS) compared with the non-injection groups (Lw-N and Ow-N). VAS was lower in the Ow-CS group than in the Lw-CS group (p < 0.05). There was no significant difference in WOMAC between the intra-articular chitosan injection and non-injection groups at each time point (Lw-N vs. Lw-CS, Ow-N vs. Ow-CS, p > 0.05). CONCLUSION: Arthroscopic surgery combined with intra-articular chitosan injection shows short-term positive effects in treating KOA. Intra-articular chitosan injection appears to have a greater short-term pain relief effect in obese patients.

Development and evaluation of an injectable ChitHCl-MgSO4-DDA hydrogel for bone regeneration: In vitro and in vivo studies on cell migration and osteogenesis enhancement.

Nonunion and delayed union of the bone are situations in orthopedic surgery that can occur even if the bone alignment is correct and there is sufficient mechanical stability. Surgeons usually apply artificial bone grafts in bone fracture gaps or in bone defect sites for osteogenesis to improve bone healing; however, these bone graft materials have no osteoinductive or osteogenic properties, and fit the morphology of the fracture gap with difficulty. In this study, we developed an injectable chitosan-based hydrogel with MgSO4 and dextran oxidative, with the purpose to improve bone healing through introducing an engineered chitosan-based hydrogel. The developed hydrogel can gelate and fit with any morphology or shape, has good biocompatibility, can enhance the cell-migration capacity, and can improve extracellular calcium deposition. Moreover, the amount of new bone formed by injecting the hydrogel in the bone tunnel was assessed by an in vivo test. We believe this injectable chitosan-based hydrogel has great potential for application in the orthopedic field to improve fracture gap healing.