Anti-inflammatory peptide therapeutics and the role of sulphur containing amino acids (cysteine and methionine) in inflammation suppression: A review.

BACKGROUND: Inflammation serves as our body's immune response to combat infections, pathogens, viruses, and external stimuli. Inflammation can be classified into two types: acute inflammation and chronic inflammation. Non-steroidal anti-inflammatory medications (NSAIDs) are used to treat both acute and chronic inflammatory disorders. However, these treatments have various side effects such as reduced healing efficiency, peptic ulcers, gastrointestinal toxicities, etc. METHOD: This review assesses the potential of anti-inflammatory peptides (AIPs) derived from various natural sources, such as algae, fungi, plants, animals, and marine organisms. Focusing on peptides rich in cysteines and methionine, sulphur-containing amino acids known for their role in suppression of inflammation. RESULT: Due to their varied biological activity, ability to penetrate cells, and low cytotoxicity, bioactive peptides have garnered interest as possible therapeutic agents. The utilisation of AIPs has shown great potential in the treatment of disorders associated with inflammation. AIPs can be obtained from diverse natural sources such as algae, fungi, plants, and animals. Cysteine and methionine are sulphur-containing amino acids that aid in the elimination of free radicals, hence assisting in the treatment of inflammatory diseases. CONCLUSION: This review specifically examines several sources of AIPs including peptides that contain numerous cysteines and methionine. In addition, the biological characteristics of these amino acids and advancements in peptide delivery are also discussed.

A review on current advancement in zebrafish models to study chronic inflammatory diseases and their therapeutic targets.

Chronic inflammatory diseases are caused due to prolonged inflammation at a specific site of the body. Among other inflammatory diseases, bacterial meningitis, chronic obstructive pulmonary disease (COPD), atherosclerosis and inflammatory bowel diseases (IBD) are primarily focused on because of their adverse effects and fatality rates around the globe in recent times. In order to come up with novel strategies to eradicate these diseases, a clear understanding of the mechanisms of the diseases is needed. Similarly, detailed insight into the mechanisms of commercially available drugs and potent lead compounds from natural sources are also important to establish efficient therapeutic effects. Zebrafish is widely accepted as a model to study drug toxicity and the pharmacokinetic effects of the drug. Moreover, researchers use various inducers to trigger inflammatory cascades and stimulate physiological changes in zebrafish. The effect of these inducers contrasts with the type of zebrafish used in the investigation. Hence, a thorough analysis is required to study the current advancements in the zebrafish model for chronic inflammatory disease suppression. This review presents the most common inflammatory diseases, commercially available drugs, novel therapeutics, and their mechanisms of action for disease suppression. The review also provides a detailed description of various zebrafish models for these diseases. Finally, the future prospects and challenges for the same are described, which can help the researchers understand the potency of the zebrafish model and its further exploration for disease attenuation.

Insights on the mechanism of bleomycin to induce lung injury and associated in vivo models: A review.

Acute lung injury leads to the development of chronic conditions such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), asthma as well as alveolar sarcoma. Various investigations are being performed worldwide to understand the pathophysiology of these diseases, develop novel bioactive compounds and inhibitors to target the ailment. Generally, in vivo models are used to understand the disease outcome and therapeutic suppressing effects for which the animals are chemically or physically induced to mimic the onset of definite disease conditions. Amongst the chemical inducing agents, Bleomycin (BLM) is the most successful inducer. It is reported to target various receptors and activate inflammatory pathways, cellular apoptosis, epithelial mesenchymal transition leading to the release of inflammatory cytokines, and proteases. Mice is one of the most widely used animal model for BLM induced pulmonary associated studies apart from rat, rabbit, sheep, pig, and monkey. Although, there is considerable variation amongst in vivo studies for BLM induction which suggests a detailed study on the same to understand the mechanism of action of BLM at molecular level. Hence, herein we have reviewed various chemical inducers, mechanism of action of BLM in inducing lung injury in vivo, its advantages and disadvantages. Further, we have also discussed the rationale behind various in vivo models and recent development in BLM induction for various animals.

Alginate-based drug carrier systems to target inflammatory bowel disease: A review.

Inflammatory bowel disease (IBD) is an inflammatory disorder that affects the gastrointestinal tract. IBD has become an increasingly common condition in both developed and developing nations over the last few decades, owing to a variety of factors like a rising population and diets packed with processed and junk foods. While the root pathophysiology of IBD is unknown, treatments are focused on medications aimed to mitigate symptoms. Alginate (AG), a marine-derived polysaccharide, is extensively studied for its biocompatibility, pH sensitivity, and crosslinking nature. This polymer is thoroughly researched in drug delivery systems for IBD treatment, as it is naturally available, non-toxic, cost effective, and can be easily and safely cross-linked with other polymers to form an interconnected network, which helps in controlling the release of drugs over an extended period. There are various types of drug delivery systems developed from AG to deliver therapeutic agents; among them, nanotechnology-based systems and hydrogels are popular due to their ability to facilitate targeted drug delivery, reduce dosage, and increase the therapeutic efficiency. AG-based carrier systems are not only used for the sustained release of drug, but also used in the delivery of siRNA, interleukins, and stem cells for site directed drug delivery and tissue regenerating ability respectively. This review is focussed on pathogenesis and currently studied medications for IBD, AG-based drug delivery systems and their properties for the alleviation of IBD. Moreover, future challenges are also be discoursed to improve the research of AG in the field of biopharmaceuticals and drug delivery.

Crab (Charybdis natator) exoskeleton derived chitosan nanoparticles for the in vivo delivery of poorly water-soluble drug: Ibuprofen.

The study aims to extract and purify chitosan (CS) from the exoskeleton of crab (C. natator) and develop ibuprofen (IBU) encapsulated CS nanoparticles (IBU-CSNPs). Analysis of purified CS revealed characteristic functional and crystallinity peaks. Moreover, morphological analysis of prepared IBU-CSNPs showed uniform spherical shape with a size range of 40-100 nm whereas encapsulation efficiency (EE%) and loading capacity (LC%) were estimated to be 68.94 ± 1.61% and 28 ± 1.18% respectively. Further, in vitro release profile of IBU from IBU-CSNPs was observed to be in biphasic form with initial release up to 15 h followed by the sustained release in different test conditions. Further, the effects of purified CS on the viability of RAW264.7 cells exhibited no toxic effects in higher concentrations. Furthermore, fluorescein isothiocyanate (FITC) conjugated nanoparticles (FITC-IBU-CSNPs) were investigated on in vivo model of adult zebrafish for time-dependent circulation and accumulation of the drug through the nano-carrier system. It was observed that the drug diffusion from the nanoparticles was in a sustained manner throughout the gastrointestinal region which resulted in suppression of inflammation. Overall, this study provides an effective and facile process for preparing a crab CS-based nano-carrier system used for the delivery of IBU in vivo which may help in the curing of prolonged chronic inflammatory diseases. Moreover, it may also help to reduce adverse effects of these drugs in the gastrointestinal tract such as ulcers and bleeding.

Pulmonary drug delivery applications of natural polysaccharide polymer derived nano/micro-carrier systems: A review.

Respiratory distress syndrome and pneumothorax are the foremost causes of death as a result of the changing lifestyle and increasing air pollution. Numerous approaches have been studied for the pulmonary delivery of drugs, proteins as well as peptides using meso/nanoparticles, nanocrystals, and liposomes. These nano/microcarrier systems (NMCs) loaded with drug provide better systemic as well as local action. Furthermore, natural polysaccharide-based polymers such as chitosan (CS), alginate (AG), hyaluronic acid, dextran, and cellulose are highly used for the preparation of nanoparticles and delivery of the drug into the pulmonary tract due to their advantageous properties such as low toxicity, high hydrophobicity, supplementary mucociliary clearance, mucoadhesivity, and biological efficacy. These properties ease the delivery of drugs onto the targeted site. Herein, recent advances in the natural polymer-derived NMCs have been reviewed for their transport and mechanism of action into the bronchiolar region as well as the respiratory region. Various physicochemical properties such as surface charge, size of nanocarrier system, surface modifications, and toxicological effects of these nanocarriers in vitro and in vivo are elucidated as well. Furthermore, challenges faced for the preparation of a model NMCs for pulmonary drug delivery are also discoursed.

Preparation and optimization of chitosan nanoparticles from discarded squilla (Carinosquilla multicarinata) shells for the delivery of anti-inflammatory drug: Diclofenac.

Biological waste from marine sources is discarded into various water bodies which leads to dramatic increase in the water pollution near coastal areas. This animal waste consists of bioactive compounds such as fatty acids, amino acids, and chitin which can be used in agricultural and pharmaceutical sectors. The aim of the current study was to extract chitosan (CS) from the discarded shells of Carinosquilla multicarinata and prepare anti-inflammatory drug diclofenac potassium (DP) encapsulated chitosan nanoparticles (DP-CSNPs). The CS was extracted, purified and physicochemical and morphological properties were characterized such as viscosity (1.44cPs), molecular weight (~57 kDa), degree of deacetylation (83%). The DP-CSNPs were prepared by ionic gelation of extracted chitosan with tripolyphosphate (TPP) anions by varying chitosan, TPP, and drug concentrations. SEM imaging showed that DP-CSNPs were nano-sized (248 nm) along with small, spherical, and uniformity in shape. The endothermic peak appeared at 180°C while performing the thermal analysis of DP-CSNPs by differential scanning calorimetry (DSC). The Loading capacity (LC) and encapsulation efficiency (EE) were determined for all combinations while maximum EE (79.42%), LC (42.08%), and +0.00459 mV for Zeta potential were found for nanoparticles synthesized from CS with 2.5mg/mL concentration and 1mg/mL of TPP and drug concentrations. Moreover, in vitro drug release study was performed at simulated biological fluid (pH 7.4) and at 10th hr maximum (80%) of the drug was released from DP-CSNPs. Therefore, this waste source would be a better model system for the drug release. Implications: Dumping of marine waste into deep ocean has led to dramatic increase in water pollution leading to the endangerment of various oceanic animals. This discarded waste can be used sustainably for the isolation of various biopolymers into the ultimate use for human community. The work provides a detailed guide into the method of extraction of low molecular weight chitosan and preparation of nanoparticles for the delivery of anti-inflammatory drug diclofenac.