It is also being explored as a potential medium for the delivery of radiopharmaceuticals, genes, and peptides. This substance, characterized by its weakly basic nature, doesn't readily dissolve in aqueous or typical organic solvents. However, it can disperse in slightly acidic aqueous solutions at pH of approximately 6.

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.

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