Caroline Hoemann, a professor in chemical engineering and biomedical engineering, and a biomaterials and tissue engineering specialist, wanted to remedy this situation by determining precisely how to use chitosan to preserve cartilage from degeneration. Osteoarthritis affects a large percentage of the population and can arise when cartilage, a thin layer of tissue that covers the ends of bones, becomes worn away.

Cartilage is an elastic and resilient tissue which acts as a shock absorber between the bones in the joint. In osteoarthritis, the cartilage tissue becomes worn to the bone.

Osteoarthritis can also affect the spine, fingers, ankles and, most frequently, the knees. End result: chronic pain and reduced mobility. In this setting, macrophages are the bad guys.

Cartilage, a tissue that is attached to the ends of bones in the joint, is devoid of blood vessels. Instead, it bathes in a liquid that also acts as a lubricant. Within the thin tissue that produces this liquid, macrophages are found. They have a dual purpose: to produce molecules that nourish and protect the cartilage tissue, and others that protect the knee against an infection.

Joint inflammation can develop. And when that inflammation becomes chronic, macrophages produce molecules that degrade cartilage. First, with her graduate student David Fong, they produced chitosan chains of varying length to see if this could make a difference. This intuition paid off. When macrophages encounter chitosan, it is treated like a foreign body.

When the chitosan chain is the right length, it tricks the macrophages into sensing that they are faced with a bacterium. The result is that they produce anti-inflammatory molecules such as interferon-beta and the interleukin-1 receptor antagonist.

This was not known until now. By improving our understanding of the role of inflammation in tissue regeneration, Caroline Hoemann and her team have just made a breakthrough in uncharted territory that prevented chitosan from being the anti-osteoarthritis molecule that researchers had been investigating for many years.

When it is the right chain length, chitosan stimulates the macrophages into releasing molecules that promote healing in situ, in the liquid that lubricates the cartilage surfaces. Excellent results were obtained with in-vitro, as well as in-vivo, tests.

Clinical testing in humans is envisioned in the near future. The ultimate goal? New therapies for people suffering from osteoarthritis, therapies that are available in the clinic. Founded in , Polytechnique Montréal is one of Canada's leading engineering teaching and research institutions.

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Jorge Michelle, Lúcia T. Ruiz Ana, E. Pintado Manuela and E. Carvalho Joao, Anti-Proliferative, Anti-Inflammatory, Anti-Ulcerogenic and Wound Healing Properties of Chitosan, Current Bioactive Compounds ; 12 2. Medicinal Plants, Phytomedicines and Traditional Herbal Remedies for Drug Discovery and Development against COVID Brain Tumor Targeting Drug Delivery Systems: Advanced Nanoscience for Theranostics Applications.

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Graphical Abstract. Mark Item. Current Bioactive Compounds. Title: Anti-Proliferative, Anti-Inflammatory, Anti-Ulcerogenic and Wound Healing Properties of Chitosan Volume: 12 Issue: 2 Author s : Freni K. Carvalho Affiliation: Keywords: Chitosan , wound healing , anti-ulcerative , anti-proliferative , biological properties , in vivo testing.

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Chito-oligosaccharide reduced the incidence of diarrhea, but the growth performance of E. coli -challenged pigs supplemented with mg of chito-oligosaccharide was not better than that of unsupplemented pigs challenged with E.

coli K In essence, the danger model proposes that endogenous host-derived molecules from damaged cells and tissues activate the immune system to cause a systemic inflammatory response.

Activation of the corresponding receptors in turn results in the production of pro-inflammatory and tissue-injurious mediators [20]. Toll-like receptors TLRs are an important class of pattern recognition receptors PRRs in innate immunity, and play a critical role in pathogen recognition and host defense [21].

TLR4 activation and cytokine production by intestinal epithelial cells IECs can induce the recruitment and activation of inflammatory cells, and prolonged or dysregulated pro-inflammatory cytokine production may lead to tissue damage and epithelial barrier dysfunction [22].

TLR4 plays a major role in controlling inflammation through the inhibition of mitogen-activated protein kinase p38 and c-Jun N-terminal kinase and NF-κB signaling pathways [23].

TLR4 activation has been shown to be involved in the pathogenesis of acute tissue injury and the induction of a systemic inflammatory state [24]. An important biological consequence of TLR signalling is the production of chemoattractants, which leads to the recruitment of inflammatory cells to the site of exposure [25].

Therefore, this piglet diarrhea model was useful for studying TLR4-mediated inflammatory responses in the intestine. Our earlier work showed that COS supplementation decreased the expression of TLR4 mRNA, and our current work extends these findings by demonstrating that COS supplementation decreased TLR4 protein expression, which indicates that COS supplementation can efficiently activate an inflammatory immune response, thus reducing intestinal infection.

Calprotectin is a cytosolic protein in the S protein group; its levels increase under conditions such as inflammation, infection, and malignancy. It has immunomodulatory, antimicrobial and antiproliferative action and is predominantly found in neutrophils, monocytes and macrophages, as well as to a lesser extent in T and B lymphocytes [26].

Fecal calprotectin is a promising marker of neutrophilic intestinal inflammation [27] , and correlates well with the severity of inflammation, as judged by both endoscopic and histological scoring systems [28].

It has been consistently shown to be elevated in patients with known irritable bowel disease IBD , and has an excellent negative predictive value in ruling out IBD in under-diagnosed symptomatic patients.

The degree of inflammation has been shown to be strongly associated with calprotectin-positive cells in the stomach [29]. coli elicited a significant increase in the calprotectin level, which was confirmed by immunofluorescence and immunohistochemistry, and the calprotectin level is an important indicator of inflammatory bowel disease [5].

Calprotectin is an abundant neutrophil protein that is released during inflammation. Since calprotectin correlates well with the degree of inflammation, the results of the current study demonstrated that supplementation with COS and chlortetracycline efficiently decreased calprotectin protein expression, and therefore inhibited inflammation and decreased diarrhea in piglets.

Proinflammatory cytokines emanating from the immune system can have profound effects on the neuroendocrine system, either by gaining direct access to the central nervous system or by triggering the synthesis of cytokines by cells in the central nervous system [30].

Inflammatory activation IL-1β or TNF-α of astrocytes results in the transient production of key inflammatory mediators including IL-6, cell surface adhesion molecules, and various leukocyte chemoattractants [31]. Lower levels of IL-6 help to regulate the recruitment and activity of inflammatory cells and limit inflammatory damage.

The complex network of cytokines regulates the immune response in the host to prevent susceptibility to disease and enhance resistance to infections. Logically, up-regulation of the protein expression of TLR4 should indicate that the TLR4 signaling pathway is inhibited, and its downstream cytokines including IL-1β, IL-6 and TNF-α should decrease.

However, IL-1β and IL-6 mRNA expression improved in that study. Moreover, that study supported our present study in that COS supplementation promoted IL-1β and IL-6 expression, while COS did not affect either TNF-α mRNA expression in the jejunal mucosa, or the levels of IL-1β, IL-6 and TNF-α in serum.

We can speculate on possible reasons for these results: In response to peripheral challenge with enterotoxigenic E. coli , comprehensive inflammation may have been elicited in weaned piglets; a variety of cells in the immune system may have secreted high concentrations of proinflammatory cytokines.

COS supplementation enhances the cell-mediated immune response by modulating the production of cytokines, but some time is needed before TLR4 can activate its downstream signaling pathway. Therefore, IL-1β and IL-6 mRNA expression in intestinal mucosa were still quite high when the piglets were slaughtered.

This result is consistent with a previous report that supplementation with COS and chlortetracycline have similar effects in reducing intestinal inflammation, but different effects on intestinal mucosal barrier function [18].

In summary, we can propose a mechanism by which COS can inhibit diarrhea: after chitosan adheres to the intestinal mucosa, its amine is recognized by the immune system.

Immune response pathways are activated, and the gut-associated lymphoid immune system is stimulated to produce lymphokines and inflammatory mediators, secrete cytokines IL-1, IL-6, etc. Therefore, COS helps to prevent inflammatory intestinal disorders, including weaning-associated intestinal inflammation.

Furthermore, our previous paper reported that diets supplemented with COS or chlortetracycline could improve intestinal mucosal morphology and occludin protein expression [18].

Thus, the digestion and absorption of nutrients in the intestine are improved in piglets. These may be contributing factors for chitosan to decrease diarrhea. In conclusion, we have demonstrated that supplementation with COS and chlortetracycline can decrease the occurrence of diarrhea and alleviate intestinal inflammation by up-regulating TLR4 and calprotectin protein expression in weaned piglets challenged with enterotoxigenic Escherichia coli.

In addition, COS can enhance the cell-mediated immune response by modulating the production of inflammatory cytokines. Conceived and designed the experiments: ZT YY JH CMN SWK.

Performed the experiments: DX ZF MR. Analyzed the data: XH WY. Wrote the paper: DX YW. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field.

Article Authors Metrics Comments Media Coverage Reader Comments Figures. Abstract The aim of this study was to investigate whether supplementation with chitosan COS could reduce diarrhea and to explore how COS alleviates intestinal inflammation in weaned pigs.

Introduction Weaning removes young pigs from the passive immune protection they receive from the milk of the sow and increases their susceptibility to enterotoxigenic E. Materials and Methods Animals and experimental design Animals and experimental design were same with the previous reported paper [18].

Download: PPT. Table 1. Diarrhea index The piglets' stool was observed when they were fed, and those that had thin, soft feces were considered to have diarrhea. Immunohistochemistry and relative quantitative real-time PCR Calprotectin and TLR4 protein expression in the jejunal mucosa were detected by immunohistochemistry.

Table 2. Statistical Analysis The data was analyzed by analysis of variance ANOVA using the general linear model GLM procedure of the statistical analysis system SAS programs 9.

Results Diarrhea As presented in Fig. Inflammatory cytokines The concentrations of IL-1β, IL-6 and TNF-α in serum were not affected by any of the treatments Table 3.

Table 3. Serum IL-1β, IL-6 and TNF-α levels in weaned piglets. Jejunal mucosal calprotectin and TLR4 protein expression The color signals of jejunal mucosal calprotectin and TLR4 protein expression in the COS group were lighter than those in both the control and chlortetracycline groups Figure 2.

Figure 2. Calprotectin and TLR4 protein expression in jejunal mucosa immunohistochemical staining, × Table 4. Integral optical density of Calprotectin and TLR4 protein expression in jejunal mucosa.

Jejunal mucosal IL-1β, IL-6 and TNF-α mRNA expression There was no difference in the relative expression level of jejunal mucosal TNF-α mRNA among the three groups Figure 3.

Figure 3. The relative expression of IL-1β, IL-6 and TNF-α mRNA in jejunal mucosa. Discussion The present study established an excellent piglet diarrhea model for intestinal disorder and demonstrated a clear difference between the effects of COS or chlortetracycline on intestinal inflammation.

Author Contributions Conceived and designed the experiments: ZT YY JH CMN SWK. References 1. Yin YL, Tang ZR, Sun ZH, Liu ZQ, Li TJ, et al.

Asian-Aust J Anim Sci — View Article Google Scholar 2. Fairbrother JM, Nadeau E, Gyles CL Escherichia coli in postweaning diarrhea in pigs: an update on bacterial types, pathogenesis, and prevention strategies. Anim Health Res Rev 6: 17— View Article Google Scholar 3.

Liu P, Piao XS, Thacker PA, Zeng ZK, Li PF, et al. J Anim Sci — View Article Google Scholar 4. van der Fels-Klerx HJ, Puister-Jansen LF, van Asselt ED, Burgers SL Farm factors associated with the use of antibiotics in pig production.

View Article Google Scholar 5. Splichal I, Fagerhol MK, Trebichavsky I, Splichalova A, Schulze J The effect of intestinal colonization of germ-free pigs with Escherichia coli on calprotectin levels in plasma, intestinal and bronchoalveolar lavages.

Immunobiology — View Article Google Scholar 6. von Roon AC, Karamountzos L, Purkayastha S, Reese GE, Darzi AW, et al. Am J Gastroenterol — View Article Google Scholar 7.

Heimesaat MM, Fischer A, Jahn HK, Niebergall J, Freudenberg M, et al. Gut — View Article Google Scholar 8. Tang ZR, Yin YL, Nyachoti CM, Huang RL, Li TJ, et al.

Domest Anim Endocrinol — View Article Google Scholar 9. Anandan R, Ganesan B, Obulesu T, Mathew S, Kumar RS, et al. Int J Biol Macromol — View Article Google Scholar Rabea EI, Badawy ME, Stevens CV, Smagghe G, Steurbaut W Chitosan as antimicrobial agent: applications and mode of action.

These molecules dissolve easily in water because they are smaller and have fewer bonds to break. Due to its natural cationic character and weaker hydrophobic interactions than anionic polymeric carbomers, chitosan is mucoadhesive.

Combining chitosan with other negatively charged molecules, such as inorganic or organic ionic medications, can improve the chemical, biological, or physical properties of chitosan Dongre, Cationic substructures that confer ionic interactive mucoadhesion are partially responsible for some key modifications in its skeleton.

PEGylation can modify the surface properties of chitosan, impacting its interactions with biological tissues. Thiol groups can form bonds with other molecules, influencing the overall properties of chitosan.

The combined effect of these modifications is an increase in the cationic nature of chitosan, making it more positively charged. This enhanced cationicity can improve its interaction with negatively charged mucosal surfaces mucoadhesiveness.

Overall, chitosan is a versatile mucoadhesive polymer that can be altered to improve its qualities for versatile utilization.

Rationally chosen levels of deacetylation and the molecular weight of natural chitosan were discovered to govern improved penetration and lowered toxicity in addition to somewhat increased epithelial permeability Dongre, Chemical modification of chitosan leads to the generation of various derivatives, including quaternized chitosan, thiolated chitosan, carboxylated chitosan, amphiphilic chitosan, chitosan with chelating agents, PEGylated chitosan, and lactose-modified chitosan.

These modifications involve reactions with sulfates, citrates, and phosphates, thereby enhancing stability and drug encapsulation efficiency Lodi et al. For instance, to address the solubility of chitosan in intestinal media, N-trimethyl chitosan chloride TMC , a quaternized chitosan, has been synthesized Ghume, V.

The two variants of TMC, namely TMC 40 and TMC 60, have demonstrated an improvement in the intestinal permeation of hydrophilic macromolecular drugs. Chitosan is simple to combine with other permeability enhancer doping drugs, which can result in a synergistic effective phenomenon that causes activity to increase by four times Kumar et al.

N-trimethylated chitosan derivatives combined with polyethylene glycol PEG are utilized to create hydrogels for nasal drug delivery, with consideration given to the inherent molecular weight of chitosan, categorized as low, medium, or high.

Notably, the high or moderate molecular weight chitosan, when N-trimethylated and blended with PEG, exhibits a narrower sol-gel transition range at body temperature, in addition to its strong mucoadhesive properties.

These chitosan hydrogel formulations offer several advantages, including rapid sol-gel transition at room temperature, favorable pharmacokinetics, rheological properties, and mucoadhesion.

They enable controlled and sustained drug delivery, promote stability, enhance effectiveness, and exhibit low toxicity. Within these chitosan-nanostructured frameworks, modifications involving the hydroxyl and primary amino functionalities lead to biological and physicochemical cross-linking within the matrix.

The formation of precipitates occurs due to the merging of chitosan droplets with alkaline solutions, while stable droplets are formed through emulsion and high-speed stirring, resulting from random collisions.

An additional technique involves the use of a reverse micellar medium to produce ultrafine chitosan nanoparticles with narrow particle sizes, either 1 or 10 nm, which are highly suitable for efficient drug delivery.

By utilizing surfactants dispersed in an organic medium to generate reverse micelles, this systematic encapsulation approach can be employed to incorporate various conjugates into the chitosan matrix, producing noteworthy nanoparticles for macromolecule distribution, with promising prospects in research and development Kavitha et al.

Thiolated derivatives of chitosan, such as chitosan-thioglycolic acid, chitosan-cysteine, chitosan-glutathione, and chitosan-thioethylamidine, are currently in use. NPs based on TMC-cysteine have demonstrated significantly enhanced mucoadhesion and permeation compared to TMC NPs.

The incorporation of poly methyl methacrylate through grafting carboxylated chitosan has been employed to achieve pH-sensitive properties Hanbali et al. For the treatment of cutaneous leishmaniasis, amphotericin B-loaded chitosan nanoparticles were developed.

Two variants with distinct electrical properties were prepared using positively charged sodium tripolyphosphate TPP and negatively charged dextran sulfate as crosslinkers. Both types exhibited high in vitro activity against Leishmania amastigotes.

Interestingly, amphotericin B in aqueous solution struggled to penetrate the skin. When applied to isolated mouse skin, both types of AmB-loaded chitosan nanoparticles facilitated a slow and limited penetration of AmB, achieving osmotic balance after approximately 20 hours.

This suggests that chitosan nanoparticles can enhance the in vitro skin permeation of amphotericin B. Tacrolimus-loaded chitosan nanoparticles were formulated by Salma et al. using ion gelation technology for the purpose of treating psoriasis.

The in vitro skin permeation study was conducted over a hour period. This indicates a significant ability of the chitosan nanoparticles to effectively delay the release of tacrolimus, thereby reducing the systemic toxicity of the drug. Furthermore, the skin deposition rate after 24 hours for tacrolimus cream was Atransdermal emulsion coated with chitosan containing 5-fluorouracil exhibited favorable skin permeation characteristics when compared to the 5-fluorouracil solution.

The enhanced permeation was attributed to the fluidization of the stratum corneum by chitosan and surfactants in the emulsion, as previously described by Khan et al. An investigation on impact of chitosan coating on the skin permeation properties of clotrimazole microemulsion conducted and the study involved measuring drug retention in rat skin after 8 hours of transdermal permeation.

Trombino et al. conducted research on combining cyclosporin A with chitosan carboxylate through an amidation reaction to create a prodrug. This prodrug was uniformly dispersed in a chitosan-based polymer membrane for the treatment of breast cancer.

Skin permeation experiments on porcine skin demonstrated that the model drug coumarin-6 could penetrate into the dermis, indicating penetration beyond the surface and into deeper layers of the skin, according to Trombino et al.

Hybrid nanogels that are obtained from chitosan display non-reversible pH reactivity. Additionally, quantum dots composed of chitosan-nanogel are utilized in this context. Wu et al. Chitosan-ZDV Zidovudine composite. Prevents the degradation of Zidovudine in human plasma, ensuring its long-term stability.

The composite remains in the kidney for a more extended period shelf life compared to the liver, heart, spleen, lung, and brain. Hasanjani and Zarei Andishmand, Tabibiazar, Mohammadifar, and Hamishehkar Sodium alginate- chitosan formulation.

Administration of drug through vaginal route. A composite of alginate, consisting of chitosan and sodium in a weight ratio , exhibited controlled release of the medication chlorhexidine digluconate. Abruzzo et al.

Chitosan-PEM Polyelectrolyte multilayer vascular patches. Drug delivery for vascular regeneration. Improved hemocompatibility, enhanced anti-platelet adhesion ability, prolonged in vitro coagulation time, and decreased hemolysis rate of Heparin.

Sun et al. Extraocular and transdermal delivery of drug. Improved therapeutic efficacy of challenging drugs employed for extraocular and skin diseases.

Başaran, Yenilmez, Berkman, Büyükköroğlu, and Yazan Chitosan nanospheres of 5-fluorouracil. Delivery of 5-fluorouracil for cancer therapy. These stable nanoparticles of chitosan, at a nanoscale, have the ability to transport medications to tumor cells and encapsulate them within those cells.

Dongsar et al. Chitosan- TPP Tripolyphosphate composite. Administration of Insulin for diabetes management. Chitosan enhances bioavailability and, as a result of reduced intestinal absorption, leads to lower blood sugar levels. Prabahar, Udhumansha, and Qushawy Chitosan nanostructures protect the enclosed plasma DNA from degradation by nucleases.

Mao et al. Delivery of encapsulated conjugates. Hu, Wang, Zhou, Xue, and Luo ; Jing, Diao, and Yu luorescein drug gets effective delivery, facilitating delivery of curcumin. Effective drug transport to ocular mucosal epithelium, improved therapeutic efficacy of curcumin.

Caprifico, Polycarpou, Foot, and Calabrese , Hu and Luo Inflammation represents the body's initial defensive response to infection or injury in a specific tissue region, involving a distinct group of immune and inflammatory cells. Historically, inflammation was defined based on visual observations, characterized by five cardinal signs: redness rubor , swelling tumour , heat calor , pain dolor , and loss of function functio laesa Schmid-Schönbein, The term "anti-inflammatory" pertains to drugs or therapeutic methods aimed at reducing inflammation.

Unlike opioids, which impact the central nervous system, anti-inflammatory medications constitute roughly half of analgesics and work by alleviating both pain and inflammation Dinarello, Bacterial infections can be transmitted through various means, requiring enough organisms to survive in the environment and reach a susceptible host for dissemination.

Many bacteria have adapted to endure in water, soil, food, and other settings. Some utilize vectors like animals or insects as intermediaries before infecting another human. The development of bacterial infection and disease is influenced by several factors.

Firstly, the infectivity of an organism determines the number of individuals infected relative to those susceptible and exposed. Secondly, pathogenicity gauges the potential of an infectious organism to induce disease, with pathogenic bacteria possessing traits that enable them to elude the body's defences and exploit its resources.

Lastly, virulence pertains to an organism's inclination to cause disease, encompassing features such as invasiveness and toxin production. Host factors play a crucial role in determining whether disease ensues following the transmission of a bacterial agent.

These factors encompass genetic makeup, nutritional status, age, duration of exposure to the organism, and existing illnesses. The environment also contributes to host susceptibility, with factors like air pollution, chemicals, and environmental contaminants weakening the body's defence against bacterial infections.

Viral infections can instigate widespread diseases in humans, ranging from mild to severe, often carrying the potential for fatality unless effectively managed.

Acute viral infections exhibit a sudden and rapid onset of illness, which can either be swiftly resolved by the host's robust innate immune responses or, alternatively, lead to the demise of the host.

Following viral infection, components of innate immunity, including physical barriers, diverse phagocytic cells, a group of cytokines, interferons IFNs , and IFN-stimulated genes, constitute the initial defence line for clearing the virus.

Innate immunity not only plays a crucial role in the swift elimination of viruses but can also contribute to disease progression by causing immune-mediated damage to the host's tissues. While elements of the antiviral innate immune response are equipped to counter viral invasion, viruses have evolved various strategies to evade host immune surveillance, ensuring the establishment of successful infections.

A comprehensive understanding of the intricate mechanisms governing the interaction between viruses and the host's innate immune system is essential for devising rational treatment strategies for acute viral infectious diseases.

Rai et al. Fungal infections pose a significant public health threat, especially in the context of patients with various diseases, including Covid, where they are linked to potentially life-threatening mycoses and increased mortality rates.

These infections encompass a spectrum of conditions, ranging from superficial and cutaneous to sub-cutaneous, mucosal, and systemic infections, each varying in severity. Organisms like Candida spp.

In immunocompromised patients, such as those with HIV, cancer patients undergoing chemotherapy, and individuals receiving immunosuppressive drugs, these infections can escalate to invasive candidiasis, posing a serious threat. Beyond opportunistic and systemic infections, fungal pathogens such as Candida, Aspergillus, Fusarium, Mucorales, and molds contribute to healthcare-associated infections HAI in patients with underlying illnesses.

In specific geographical regions, these fungal pathogens are responsible for prevalent and life-threatening endemic mycoses, including Blastomycosis, Coccidioidomycosis, Histoplasmosis, Talaromycosis, Paracoccidioidomycosis, and Sporotrichosis. Protozoal infections, typically confined to specific regions due to climatic conditions and the presence of intermediate hosts facilitating transmission to humans, are now being observed beyond their original geographical boundaries.

This is likely attributed to the rise in international travel and the migration of individuals from their native regions.

It is crucial to have a comprehensive understanding of these infectious diseases, especially given the association with immunosuppression, whether it be related to HIV infection, solid organ transplantation, or bone marrow transplant involving prolonged immunosuppressive drug regimens.

Such immunosuppression can lead to more severe clinical manifestations and a reduced response to specific treatments. A notable proportion of these cases has been documented in immigrants relocating from tropical countries to non-tropical regions.

It is imperative for healthcare professionals dealing with these patients to heighten their awareness of these diseases, as this can contribute to more effective management and prevention strategies. Chimelli, Microbes typically cause infections, and inflammation is regarded as one of the organism's responses to pathogens.

It is a standardized reaction and serves as a mechanism of innate immunity Hentschel et al. Table 2 gives a brief description on various types of infection that lead to inflammation.

A substantial body of knowledge has been generated concerning the applications of chitin CT , a natural biopolymer, and its N-deacetylated form, chitosan CS , across various fields. In a study conducted by researchers wherein they encapsulated melatonin within chitosan nanoparticles to enhance its effectiveness by increasing the melatonin release properties.

Anionic sodium tripolyphosphate STPP was used in the ionic gelation process to create chitosan nanoparticles. Both in-vitro and in-vivo therapeutic benefits were investigated in this study. An in-vivo analysis was carried out in an animal model specific to mice with DSS-induced ulcerative colitis, and a model including LPS-stimulated macrophages was used to assess the in-vitro therapeutic efficiency.

With an aim to improve the anti-inflammatory qualities of atorvastatin AT , improve its surface features, achieve prolonged release, and guarantee site-specific activity,a research was conducted. In this work, AT was encapsulated into AT-PLGA-CS-NPs F1 , which were chitosan-coated PLGA nanoparticles.

Following that, F1 and free Atorvastatin were added to Pluronic hydroxymethylpropyl cellulose thermosensitive gels to create formulations F2 and F3, respectively. F4 was a water-based, basic AT suspension.

These four formulations' in-vitro release profiles were investigated in the study. The examination also looked at their capacity to irritate the eyes and how well they worked to lessen the inflammation that Prostaglandin E1 PGE1 had caused in the rabbits' eyes.

An investigation was carried out on the influence of Chitosan Oligosaccharides COS on Lipopolysaccharide LPS -stimulated RAW The findings revealed that exposure to COS dose-dependently reduced the release of TNF-α and IL-6 induced by LPS into the culture medium.

Additionally, a parallel reduction in TNF-α and IL-6 at the mRNA level suggested that COS exposure lowered the transcriptional production of these cytokines. Moreover, COS exposure was shown to reduce nitric oxide NO secretion in the medium triggered by LPS.

Remarkably, the introduction of external TNF-α into the solution counteracted the reduction in IL-6 and NO levels induced by COS, suggesting that COS's anti-inflammatory impact was affected by the TNF-α pathway. They also explored the safeguarding attributes of COS in a model representing renal oxidative stress induced by glycerol-triggered acute renal failure.

This study established that COS holds antioxidative characteristics in the kidneys, alleviates the inflammatory reaction triggered by glycerol, and improves renal function..

It has been showcased the anti-inflammatory effects of chitosan oligosaccharides COS were not only influenced by the dosage but also by their molecular weight, particularly at higher dosages. The findings indicate that COS exhibits anti-inflammatory properties that vary with the dosage and, notably, the molecular weight, especially at higher levels.

The findings of a study on the preventive impact of COS chitosan oligosaccharides in LPS-induced sepsis illustrated that COS treatment reduced organ damage and enhanced survival rates in mice given an LPS lipopolysaccharide injection. After looking at inflammatory markers such neutrophil infiltration and serum levels of IL-1β and TNF-α, the researchers discovered that COS therapy decreased these cytokines.

The redox imbalance brought on by LPS-induced sepsis was also reversed by COS therapy; this condition was marked by elevated levels of malondialdehyde MDA and decreased levels of glutathione GSH and catalase CAT.

Furthermore, LPS-induced signalling pathways such as p38 mitogen-activated protein kinase and c-Jun NH 2 -terminal kinase JNK were blocked by COS treatment MAPK. An innovative chitosan nanosponge intended to enhance the transdermal delivery of Poloxamer-based drugs was introduced in Chitosan was chosen because it can loosen the tight junctions in the stratum corneum, which allows drugs to penetrate the skin more easily.

The research combined two types of chitosan with molecular weights of 3 and 10 kDa with Poloxamer using p-nitrophenyl chloroformate. The blended mixtures of these chitosan with Poloxamer in different ratios followed by a simple nanoprecipitation process transform these blends into flexible and soft nanosponges.

The chitosan nanosponges CNSs showed stability in biological buffers for up to four weeks and had no harmful effects on human dermal fibrocytes. In Franz-type diffusion cells, the CNSs significantly improved the penetration of drugs through human cadaver skin.

The 3 kDa Poloxamer exhibited the most potential as an effective carrier for enhancing transdermal drug delivery Lee et al. In , a research was conducted to investigate the impact of chitosan-based gel to promote wound healing in donkeys. Chitosan solution was prepared by dissolving 0.

The researchers then mixed one gram of Carbopol with the chitosan solution to create Chitosan gel, which was stored at ºC until needed. The specific objective of the study was to assess the effectiveness of 0. The clinical findings indicated that wounds treated with chitosan contracted at a faster rate compared to control wounds, with shoulder wounds showing quicker contraction than forearm wounds.

Furthermore, all wounds treated with chitosan fully healed with intact epidermis by the end of the experiment. A review focused on the function of chitosan in wound healing emphasized the potential of chitosan as a biomaterial attributed to its anti-inflammatory and antibacterial properties.

The review stated that effective wound dressings should be tailored to specific wound types, be cost-effective, and minimize discomfort for patients. This requires modifying their physical characteristics. While there is ample information on chitosan and modified chitosan, there is still much to explore in the context of wound healing.

Chitin nanofibers, with their potent biological activity, have been proposed for various biomedical applications. For example, they inhibit NF-κB and MCP-1 activation, exerting anti-inflammatory effects. They also hinder fibrosis in a mouse model of acute ulcerative colitis.

These findings suggest that chitin nanofibers could be a novel therapeutic option or functional dietary component for people with inflammatory bowel disease Gokarneshan, In a murine model of acute ulcerative colitis caused by dextran sulphate sodium DSS , Kazuo Azuma and colleagues evaluated the anti-inflammatory and anti-fibrosis characteristics of α-chitin nanofibrils.

According to the study's results, α-chitin nanofibrils decreased the regions in colon tissue that showed positive nuclear factor-B staining measured at 7. Furthermore, α-chitin nanofibrils also inhibited the increased positive areas seen in Masson's trichrome staining in colon tissue 6.

In contrast, the α-chitin powder suspension did not exhibit these changes in the DSS-induced acute ulcerative colitis mouse model. The study's ultimate conclusion was that α-chitin nanofibrils possess anti-inflammatory attributes by inhibitng NF-B activation and anti-fibrogenic effects in the DSS-induced acute ulcerative colitis mouse model Azuma et al.

Ameliorated immunosuppressive micro environment to promote anti tumor effects. High drug concentration at target site and highly effective in supressing tumor growth. Minimised side effects and improved therapeutic efficacy.

Targeted tumour extracellular drug release. Prolonged circulation in blood and reduced distribution to other tissues. Site specific breast tumor micro environment drug release.

pH dependent drug release in an acidic tumor environment. Another study in explored chitosan-based scaffolds for bone regeneration, focusing on their osteoinductive and anti-inflammatory properties. The research involved assessing the ability of these scaffolds to reduce inflammation in human mesenchymal stem cells hMSCs triggered by lipopolysaccharide LPS.

Specific interleukins and oxidative stress byproducts IL-1β, IL, and nitrites related to the immune response were measured. Additionally, the scaffolds were tested in an in-vitro co-culture model mimicking inflammation in osteoporotic sites, involving osteoblasts and LPS-stimulated macrophages.

The findings revealed that these bioactivated scaffolds can: i suppress the production of inflammatory substances like IL-1β; ii decrease oxidative stress byproducts; and iii enhance the production of anti-inflammatory markers IL in hMSCs. Importantly, these bioactivated scaffolds also demonstrated anti-inflammatory effects in in-vitro co-culture systems resembling the compromised bone environment in-vivo Fasolino et al.

To evaluate chitosan's effectiveness as a pharmacological agent for treating inflammatory bowel diseases IBD with a focus on its anti-inflammatory properties, a study was implemented. The study assessed the effects of 5-aminosalicylic acid 5-ASA and the molecular weight MW and degree of deacetylation DD of chitosan in murine experimental colitis.

Over the course of three days, chitosan grades with varying MW and DD were administered via rectal route to mice suffering from colitis, either alone or in combination with 5-ASA. Myeloperoxidase MPO , alkaline phosphatase ALP , tumour necrosis factor TNF , interleukin-6 IL-6 , interleukin-1 IL-1 , and nuclear factor kappa-B NF-κB levels in the colon were then evaluated by the researchers.

Crucially, the anti-inflammatory characteristics of chitosan were not significantly affected by its unique properties, such as DD and MW. The study suggests that chitosan can be utilized together with NSAIDs to enhance its anti-inflammatory activity, particularly when combined with 5-ASA Jhundoo et al.

A research focused on investigating the impact of chitosan-alginate nanoparticles NPs on inflammatory cytokines and chemokines produced by P.

acnes was carried out where human monocytes were activated with P. acnes and subjected to different concentrations of chitosan-alginate NPs after being extracted from peripheral blood.

The study revealed that chitosan-alginate NPs effectively suppressed the formation of the inflammatory cytokine ILp40, which has a significant impact in the acne-related inflammatory response, in a dose-dependent manner. At the maximum concentration of chitosan-alginate NPs tested, there was nearly complete inhibition of IL protein.

Similarly, when human keratinocyte HaCaT cells were exposed to P. acnes in the presence of different concentrations of chitosan-alginate NPs, the study demonstrated that even at low doses, the NPs significantly prevented the initiation of IL-6 by P.

acnes in keratinocytes. Importantly, chitosan-alginate NPs showed no harmful effects on human monocytes, unlike the toxic impact of the positive control, sodium chromate, on human monocytes.

Moreover, the mild toxicity of NPs on HaCaT cells at higher concentrations was minimal compared to typical amounts of benzoyl peroxide BP used in preclinical settings. These results imply that cytokine generation produced by P. acnes in human monocytes and keratinocytes may be inhibited by chitosan-alginate nanoparticles without cytokine release as a result of cell death Friedman et al.

To explore the anti-inflammatory, wound healing, and anti-ulcerogenic properties of chitosan, an in-vivo investigation was carried out.

The experiment was conducted in Wistar rats and Swiss adult mice. In this study, Swiss adult mice Mus musculus with body weights ranging from 30 to 40 g were randomly assigned to six groups, each consisting of eight animals, for the investigation.

The experiment involved giving different types of chitosan low molecular weight, high molecular weight, and commercial to groups III to V at different concentrations 0. The chitosan was dissolved in acetone. Acetone was introduced to Group I as negative control.

Simultaneously, all animals received 20 µl of acetone on the inner surface of their left ear. After 4 hours, the animals were humanely euthanized by cervical dislocation, and standard sections measuring 6 mm in diameter were excised from both ears and weighed individually.

Croton oil-induced edema was determined as the weight difference right ear - left ear for each animal, expressed in percentage, with the results presented as the average for each group.

The research revealed that high molecular weight HMW chitosan played a role in preserving the stomach lining, providing gastroprotective benefits, while low molecular weight LMW chitosan notably reduced ethanol-induced ulcerative ulcers.

These results suggest that chitosan could have practical applications in peptic ulcer management. Chitosan being a biocompatible, biodegradable natural polysaccharide, and its non-immunogenic and nontoxic nature has potential in treating various types of tumours.

This review has highlighted the promising role of chitosan as an anti-inflammatory agent. Chitosan, a natural biopolymer derived from chitin, exhibits a broad range of anti-inflammatory properties. It has been shown to mitigate inflammation through various mechanisms, such as modulating cytokine expression, scavenging free radicals, and regulating immune responses.

The versatility of chitosan, its biocompatibility, and minimal side effects make it a valuable candidate for the development of anti-inflammatory therapies. Nevertheless, further research is required to perfectly comprehend its precise mechanisms of action and optimize its applications.

As our understanding of chitosan's anti-inflammatory potential deepens, it opens doors to innovative approaches for managing inflammatory conditions, providing hope for enhanced treatments and a better quality of life for individuals suffering from such ailments.

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Editorial Board Editorial Office and Publisher Ownership Article Processing Charge Open Access and Licensing Personal Data Protection Terms and Conditions: Cookie policy and Privacy policy Copyright and Copyright Transfer Agreement Publication Ethics and Malpractice Policy Ethics approval and informed consent Visagaa Publishing House Repository Policy Visagaa Publishing House CrossMark Policy The Initiative for Open Citations I4OC Archiving Plagiarism Policy.

Online first. Current issue. For authors Instructions for Authors. For reviewers The peer-review process Recognition for Reviewers. About the Journal Editorial Board Editorial Office and Publisher Ownership Article Processing Charge Open Access and Licensing Personal Data Protection Terms and Conditions: Cookie policy and Privacy policy Copyright and Copyright Transfer Agreement Publication Ethics and Malpractice Policy Ethics approval and informed consent Visagaa Publishing House Repository Policy Visagaa Publishing House CrossMark Policy The Initiative for Open Citations I4OC Archiving Plagiarism Policy.

Visagaa Author Services. eISSN: Chitosan a natural anti-inflammatory and wound healing agent: A brief update. Preethi Sudheer 1. Applications of Natural Resources.

Inflammation is a complex physiological response that serves as a critical component in the pathogenesis of various diseases. Over the years, chitosan, a natural polysaccharide sourced from chitin, has gained significant attention as a prospective anti-inflammatory agent.