Formulation and Development of Novel Sulfasalazine Bilayer Tablets for The Treatment of Arthritis Associated With IBD: In-vitro and In-vivo Investigations.

Sulfasalazine needs frequent daily dosing and the administration of numerous tablets per day pose challenges to patient compliance, contributing to increased adverse effects and difficulties in disease control. These inconveniences result in less effective treatment for arthritis associated with inflammatory bowel disease i.e. ulcerative colitis etc. To improve drug bioavailability, a delayed-release mechanism that releases the drug at the colon is necessary. To develop and optimize colon-targeted controlled release bilayer tablets coated with pH-dependent polymers. The bilayer tablets containing the immediate release part and sustained release part were developed. The tablets were coated with enteric-coated with Eudragit® S-100 and l-100 to achieve release in the colon. Granule properties and tablets were evaluated. The physicochemical parameters of the tablets were evaluated including, stability study, and drug release in 0.1 N HCl (pH 1.2), pH 6.8 phosphate buffer, pH 7.4 phosphate buffer for 2, 1, and up to 24 h respectively. Radiographic imaging and in vivo pharmacokinetic studies were also done in Rabbits. The bilayer tablets containing immediate and sustained release were successfully developed for the colon targeting. The granule properties were found within the acceptable range indicating good flow properties. The physicochemical properties of the tablets were also found acceptable. The tablets did not show release in 0.1 N HCl and 6.8 phosphate buffer but drug release was found under control in the 7.4 pH buffer. Sulfasalazine coated bilayer tablets were found stable and no significant changes were observed in the stability studies. Based on the X-ray studies, the formulated tablet remained discernible in the stomach, small intestine, and colon for a duration of up to 24 h. Finally, by the 32nd hour, the tablet was no longer visible in the X-ray examination, leading to the conclusion of complete drug release. The drug concentration in plasma remained within the therapeutic range for up to 24 h in vivo. These novel formulations present substantial advantages, providing prolonged targeted drug release and reducing systemic adverse effects. The results suggest promising potential for treating arthritis in Inflammatory bowel disease (IBD) patients, offering a solution to current delivery systems.

Biological macromolecules-based nanoformulation in improving wound healing and bacterial biofilm-associated infection: A review.

A chronic wound is a serious complication associated with diabetes mellitus and is difficult to heal due to high glucose levels, oxidative stress, and biofilm-associated microbial infection. The structural complexity of microbial biofilm makes it impossible for antibiotics to penetrate the matrix, hence conventional antibiotic therapies became ineffective in clinical settings. This demonstrates an urgent need to find safer alternatives to reduce the prevalence of chronic wound infection associated with microbial biofilm. A novel approach to address these concerns is to inhibit biofilm formation using biological-macromolecule based nano-delivery system. Higher drug loading efficiency, sustained drug release, enhanced drug stability, and improved bioavailability are advantages of employing nano-drug delivery systems to prevent microbial colonization and biofilm formation in chronic wounds. This review covers the pathogenesis, microbial biofilm formation, and immune response to chronic wounds. Furthermore, we also focus on macromolecule-based nanoparticles as wound healing therapies to reduce the increased mortality associated with chronic wound infections.

Association between obesity, inflammation and insulin resistance: Insights into signaling pathways and therapeutic interventions.

Obesity, a metabolic disorder, is becoming a worldwide epidemic that predominantly increases the risk for various diseases including metabolic inflammation, insulin resistance, and cardiovascular diseases. However, the mechanisms that link obesity with other metabolic diseases are not completely understood. In obesity, various inflammatory pathways that cause inflammation in adipose tissue of an obese individual become activated and exacerbate the disease. Obesity-induced low-grade metabolic inflammation perturbates the insulin signaling pathway and leads to insulin resistance. Researchers have identified several pathways that link the impairment of insulin resistance through obesity-induced inflammation like activation of Nuclear factor kappa B (NF-κB), suppressor of cytokine signaling (SOCS) proteins, cJun-N-terminal Kinase (JNK), Wingless-related integration site (Wnt), and Toll-like receptor (TLR) signaling pathways. In this review article, the published studies have been reviewed to identify the potential and influential role of different signaling pathways in the pathogenesis of obesity-induced metabolic inflammation and insulin resistance along with the discussion on potential therapeutic strategies. Therapies targeting these signaling pathways show improvements in metabolic diseases associated with obesity, but require further testing and confirmation through clinical trials.

COVID-19 and Diabetes: will Novel Drugs for Diabetes Help in COVID-19?

COVID-19 is caused by the SARS-CoV-2 virus, which has afflicted more than 245.37 million individuals worldwide and resulted in more than 4.9 million deaths as of today, with a mortality rate of 2.1%. Diabetes mellitus (DM) and its secondary complications are the major serious global health concerns today due to its growth rate, and it is the fastest-growing non-communicable disease. According to International Diabetes Federation (IDF) data, one out of 11 adults is diabetic, and the projection says that the figure will reach 642 million by 2040 globally. The occurrence of DM and its secondary complications is also associated with the severity of COVID-19 and high mortality. People with DM have a weakened immune system owing to innate immunity defects affecting phagocytosis, neutrophil chemotaxis, and cellmediated immunity; however, the high prevalence of diabetes in serious cases of COVID-19 may reflect the higher prevalence of type 2 DM (T2DM) in older people. Moreover, DM is linked to cardiovascular illness in older people, which could underlie the correlation between COVID-19 and fatal outcomes. SARS-CoV-2 infects via the angiotensin-converting enzyme 2 (ACE2), which is found in pancreatic islets, and infection with SARS-CoV-1 has been linked to hyperglycemia in individuals who do not have DM. And hence diabetic patients need to take more precautions and maintain their blood glucose levels. Many pieces of research say that COVID-19 and DM, especially its secondary complications are interlinked. But it also needs more elaborative evidence on whether the anti-diabetic drugs can manage only blood glucose or SARS-CoV-2.

Diabetic Nephropathy: Pathogenesis to Cure.

Diabetic nephropathy (DN) is a leading cause of end-stage renal disorder (ESRD). It is defined as the increase in urinary albumin excretion (UAE) when no other renal disease is present. DN is categorized into microalbuminuria and macroalbuminuria. Factors like high blood pressure, high blood sugar levels, genetics, oxidative stress, hemodynamic and metabolic changes affect DN. Hyperglycemia causes renal damage through activating protein kinase C (PKC), producing advanced end glycation products (AGEs) and reactive oxygen species (ROS). Growth factors, chemokines, cell adhesion molecules, inflammatory cytokines are found to be elevated in the renal tissues of the diabetic patient. Many different and new diagnostic methods and treatment options are available due to the increase in research efforts and progression in medical science. However, until now, no permanent cure is available. This article aims to explore the mechanism, diagnosis, and therapeutic strategies in current use for increasing the understanding of DN.

Epigenetics: key to improve delayed wound healing in type 2 diabetes.

Diabetes-related delayed wound healing is a multifactorial, nuanced, and intertwined complication that causes substantial clinical morbidity. The etiology of diabetes and its related microvascular complications is affected by genes, diet, and lifestyle factors. Epigenetic modifications such as DNA methylation, histone modifications, and post-transcriptional RNA regulation (microRNAs) are subsequently recognized as key facilitators of the complicated interaction between genes and the environment. Current research suggests that diabetes-persuaded dysfunction of epigenetic pathways, which results in changed expression of genes in target cells and cause diabetes-related complications including cardiomyopathy, nephropathy, retinopathy, delayed wound healing, etc., which are foremost drivers to diabetes-related adverse outcomes. In this paper, we discuss the role of epigenetic mechanisms in controlling tissue repair, angiogenesis, and expression of growth factors, as well as recent findings that show the alteration of epigenetic events during diabetic wound healing.

Mudbank off Alleppey, India: A bane for foraminifera but not so for carbon burial.

Calm conditions and extensive fishing, during monsoon season in the mudbank off Alleppey (Kerala), India creates a unique environment, associated with high suspended particulate matter. The effect of processes associated with mudbank formation, on benthic foraminifera, however, has not been documented. We have studied, seasonal foraminiferal distribution, to understand foraminiferal response to physico-chemical changes associated with the mudbank formation. Additionally, seasonal changes in total carbon, calcium carbonate (CaCO3), organic carbon (Corg) and Corg/nitrogen (Corg/N) were also measured to understand the effect of mudbank formation on carbon burial. We report a low foraminiferal abundance in the mudbank. Benthic foraminiferal diversity is also low in the mudbank, during both pre-monsoon and monsoon season, clearly suggesting a stressed environment. Agglutinated foraminifera dominate the living benthic foraminiferal population in the mudbank, suggesting that the area is carbonate undersaturated and under fresh-water influence. Ammobaculites dilatatus and Ammobaculites exiguus are the dominant agglutinated species abundant in the mudbank and thus can be used to reconstruct past changes in the mudbank. The CaCO3 is consistently low during all seasons, at one of the core mudbank stations. The %Corg is, however, higher in the core mudbank as well as the northern peripheral region. The Corg/N is consistently uniform at all the stations indicating a similar source of organic matter in all the seasons. The higher %Corg and constant Corg/N suggest, that food availability and its source is not a major factor affecting benthic foraminifera in the mudbank. Instead, increased turbidity and low bottom water salinity are the main cause of seasonally stressed environment in the mudbank. Additionally, Corg degradation coupled with fresh water influx induced drop in bottom water pH is responsible for low foraminiferal population in mudbank region, in all the seasons. The reduced calcareous benthic foraminiferal abundance, however, does not affect the carbon burial in the mudbank, due to higher %Corg.

Development and characterization of colon specific drug delivery system bearing 5-ASA and Camylofine dihydrochloride for the treatment of ulcerative colitis.

The treatment of ulcerative colitis (inflammatory bowel disease, IBD) has been achieved by using colon specific drug delivery system bearing 5-ASA and Camylofine dihydrochloride. Chitosan microspheres were prepared separately for both the drugs using emulsion method followed by enteric coating with EudragitS-100. The in vitro drug release was investigated in different simulated GIT medium. The drug release in PBS (pH7.4) and simulated gastric fluid has shown almost similar pattern and rate, whereas a significant increase in drug release (70.3 +/- 1.36 and 72.5 +/- 1.33% of 5-ASA and Camylofine, respectively) was observed in medium containing 3% rat caecal matter, after 24 h. In control study, 57.1 +/- 1.13% of 5-ASA and 59.2 +/- 1.2% of Camylofine release was observed in 24 h. For enzyme induction, rats were orally administered with 1 mL of 1% w/v dispersion of chitosan for 5 days and release rate studies were conducted in SCF with 3% w/v of caecal matter. An enhanced drug release (i.e., 92.3 +/- 3.81 and 95.5 +/- 3.52% 5-ASA and Camylofine, respectively) was observed after 24 h in dissolution medium containing 3% caecal content obtained from enzyme induced animals. In vivo data showed that microspheres delivered most of its drug load (76.55 +/- 2.13%) to the colon after 9 h, which reflects its targeting potential to the colon. It is concluded that orally administered microspheres of both drugs can be used together for the specific delivery of drug to the colon and reduce symptoms of ulcerative colitis.