Film Coating of Phosphorylated Mandua Starch on Matrix Tablets for pH-Sensitive Release of Mesalamine.

Chemically modified mandua starch was successfully synthesized and applied to coat mesalamine-loaded matrix tablets. The coating material was an aqueous dispersion of mandua starch modified by sodium trimetaphosphate and sodium tripolyphosphate. To investigate the colon-targeting release competence, chemically modified mandua starch film-coated mesalamine tablets were produced using the wet granulation method followed by dip coating. The effect of the coating on the colon-targeted release of the resultant delivery system was inspected in healthy human volunteers and rabbits using roentgenography. The results show that drug release was controlled when the coating level was 10% w/w. The release percentage in the upper gastric phase (pH 1.2, simulated gastric fluid) was less than 6% and reached up to 59.51% w/w after 14 h in simulated colonic fluid. In addition to in vivo roentgenographic studies in healthy rabbits, human volunteer studies proved the colon targeting efficiency of the formulation. These results clearly demonstrated that chemically modified mandua starch has high effectiveness as a novel aqueous coating material for controlled release or colon targeting.

Continuing or stopping 5-aminosalicylates in patients with inflammatory bowel disease on anti-TNF therapy: A nationwide population-based study.

BACKGROUND: The impact of continuing or stopping 5-aminosalicylates (5-ASA) after commencing anti-tumour necrosis factor (anti-TNF) therapy in patients with inflammatory bowel disease (IBD) remains unclear. AIMS: To compare the outcomes of patients with IBD who stopped or continued 5-ASA after starting anti-TNF therapy. METHODS: We analysed data from the Korean National Health Insurance claims database between 2007 and 2020. We compared the clinical outcomes of patients who stopped or continued 5-ASA within 90 days of anti-TNF initiation. The primary outcome was any adverse clinical event defined as a composite of new corticosteroid use, IBD-related hospitalisation, or intestinal surgery. RESULTS: Among 7442 patients included for analysis (4479 [60.2%] with Crohn's disease [CD] and 2963 [39.8%] with ulcerative colitis [UC]), 1037 (13.9%) discontinued 5-ASA within 90 days of starting anti-TNF therapy. During a median 4.3-year follow-up, discontinuation of 5-ASA was not associated with an increased risk of adverse clinical events (adjusted hazard ratio 1.01, 95% confidence interval 0.93-1.10). The cumulative incidence of each adverse clinical event and the composite outcome were not significantly different between groups (all, p > 0.05). Additionally, separate analyses in CD and UC cohorts revealed no differences in adverse clinical outcomes between the 5-ASA continuation and discontinuation groups. Subgroup analyses by presumed risk factors for disease relapse showed no significant differences in the risk of adverse events between groups. CONCLUSIONS: In this nationwide population-based study, discontinuing 5-ASA after starting anti-TNF therapy was not associated with an increased risk of adverse events in patients with IBD.

Downregulation of OATP2B1 by proinflammatory cytokines leads to 5-ASA hyposensitivity in Ulcerative colitis.

5-Aminosalicylic acid (5-ASA) is a first-line agent in both remission and maintenance therapy for ulcerative colitis (UC). However, the mucosal concentration of 5-ASA was significantly lower in patients with severe histological inflammation, which further led to a poor response to 5-ASA treatment. Our study aimed to clarify the mechanism of 5-ASA uptake into colonic epithelial cells and to further explore the reason for the decreased colonic mucosal 5-ASA concentration in UC patients. Our results demonstrated that the colonic 5-ASA concentration was notably reduced in DSS-induced colitis mice and inversely correlated with colonic inflammation. 5-ASA was not a substrate of carnitine/organic cation transporter 1/2 (OCTN1/2) or multidrug resistance protein 1 (MDR1), whereas organic anion transporting polypeptide 2B1 (OATP2B1) and sodium-coupled monocarboxylate transporter 1 (SMCT1) mediated the uptake of 5-ASA, with a greater contribution from OATP2B1 than SMCT1. Inhibitors and siRNAs targeting OATP2B1 significantly reduced 5-ASA absorption in colonic cell lines. Moreover, OATP2B1 expression was dramatically downregulated in colon tissues from UC patients and dextran sodium sulfate (DSS)-induced colitis mice, and was also negatively correlated with colonic inflammation. Mechanistically, mixed proinflammatory cytokines downregulated the expression of OATP2B1 in a time- and concentration-dependent manner through the hepatocyte nuclear factor 4 α (HNF4α) pathway. In conclusion, OATP2B1 was the pivotal transporter involved in colonic 5-ASA uptake, which indicated that inducing OATP2B1 expression may be a strategy to promote 5-ASA uptake and further improve the concentration and anti-inflammatory efficacy of 5-ASA in UC.

Mucoadhesive Mesalamine Prodrug Nanoassemblies to Target Intestinal Macrophages for the Treatment of Inflammatory Bowel Disease.

While mesalamine, a 5-aminosalicylic acid (5-ASA), is pivotal in the management of inflammatory bowel disease (IBD) through both step-up and top-down approaches in clinical settings, its widespread utilization is limited by low bioavailability at the desired site of action due to rapid and extensive absorption in the upper gastrointestinal (GI) tract. Addressing mesalamine's pharmacokinetic challenges, here, we introduce nanoassemblies composed exclusively of a mesalamine prodrug that pairs 5-ASA with a mucoadhesive and cathepsin B-cleavable peptide. In an IBD model, orally administered nanoassemblies demonstrate enhanced accumulation and sustained retention in the GI tract due to their mucoadhesive properties and the epithelial enhanced permeability and retention (eEPR) effect. This retention enables the efficient uptake by intestinal pro-inflammatory macrophages expressing high cathepsin B, triggering a burst release of the 5-ASA. This cascade fosters the polarization toward an M2 macrophage phenotype, diminishes inflammatory responses, and simultaneously facilitates the delivery of active agents to adjacent epithelial cells. Therefore, the nanoassemblies show outstanding therapeutic efficacy in inhibiting local inflammation and contribute to suppressing systemic inflammation by restoring damaged intestinal barriers. Collectively, this study highlights the promising role of the prodrug nanoassemblies in enhancing targeted drug delivery, potentially broadening the use of mesalamine in managing IBD.

Banxia Xiexin decoction combined with 5-ASA protects against CPT-11-induced intestinal dysfunction in rats via inhibiting TLR4/NF-κB signaling pathway.

BACKGROUND: Banxia Xiexin decoction (BXD) can control irinotecan (CPT-11)-caused delayed diarrhea, but the corresponding mechanism remains undefined. AIMS: This paper aimed to uncover the mechanism of BXD in regulating CPT-11-caused delayed diarrhea. MATERIALS & METHODS: Sprague-Dawley (SD) rats were assigned into the control, model, BXD low-dose (BXD-L, 5 g/kg), BXD medium-dose (BXD-M, 10 g/kg), BXD high-dose (BXD-H, 15 g/kg), 5-aminosalicylic acid (5-ASA, 10 mL/kg), and BXD-M + 5-ASA groups. Rats were injected intraperitoneally with 150 mg/kg CPT-11 at Day 4 and Day 5 to induce delayed diarrhea, and later treated with various doses (low, medium, and high) of BXD and 5-ASA for 9 days, except for rats in control group. The body weight of rats was measured. The rat colon tissue injury, inflammatory cytokine levels, and the activation of toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling pathway were detected. RESULTS: BXD (5, 10, or 15 g/kg) or 5-ASA (10 mL/kg) alleviated body weight loss and colon tissue injury, decreased levels of inflammatory cytokines, and inactivated TLR4/NF-κB signaling pathway in CPT-11-induced model rats. BXD at 10 g/kg (the optimal concentration) could better treat CPT-11-induced intestinal dysfunction, as evidenced by the resulting approximately 50% reduction on injury score of model rats. Moreover, BXD-M (10 g/kg) synergistic with 5-ASA (10 mL/kg) further strengthened the inhibition on rat body weight loss, colon tissue injury, inflammatory cytokine levels, and TLR4/NF-κB signaling pathway. CONCLUSION: To sum up, BXD has a protective effect against CPT-11-induced intestinal dysfunction by inhibiting inflammation through inactivation TLR4/NF-κB signaling pathway. In particular, the combined use of BXD and 5-ASA holds great promise for treating CPT-11-induced delayed diarrhea.

Perimyocarditis in a Patient with Ulcerative Colitis Treated with 5-Aminosalicylic Acid.

5-Aminosalicylic acid (5-ASA) is recommended for managing ulcerative colitis. Common adverse effects associated with 5-ASA include gastrointestinal disorders, headaches, and skin rashes. Perimyocarditis induced by 5-ASA is a rare adverse effect, with only a limited number of cases reported. This paper presents a case of 5-ASA-induced perimyocarditis in a 29-year-old female who had been taking 5-ASA for three weeks. The patient was admitted to the emergency department with dyspnea, chest discomfort, and fever. She subsequently underwent laboratory investigations, including electrocardiography, transthoracic echocardiography, chest computed tomographic angiography, cardiac magnetic resonance imaging, and heart biopsy. Intravenous steroid was administered, and 5-ASA was discontinued. The patient's signs and symptoms improved significantly within a few days of discontinuing 5-ASA, leading to her subsequent discharge. This case highlights the importance of considering perimyocarditis in patients exhibiting cardiac symptoms during 5-ASA therapy, despite it being a rare adverse effect. Drug withdrawal in such cases may lead to rapid clinical improvement.

Simultaneous Treatment of 5-Aminosalicylic Acid and Treadmill Exercise More Effectively Improves Ulcerative Colitis in Mice.

Ulcerative colitis (UC) is characterized by continuous mucosal ulceration of the colon, starting in the rectum. 5-Aminosalicylic acid (5-ASA) is the main therapy for ulcerative colitis; however, it has side effects. Physical exercise effectively increases the number of anti-inflammatory and anti-immune cells in the body. In the current study, the effects of simultaneous treatment of treadmill exercise and 5-ASA were compared with monotherapy with physical exercise or 5-ASA in UC mice. To induce the UC animal model, the mice consumed 2% dextran sulfate sodium dissolved in drinking water for 7 days. The mice in the exercise groups exercised on a treadmill for 1 h once a day for 14 days after UC induction. The 5-ASA-treated groups received 5-ASA by enema injection using a 200 µL polyethylene catheter once a day for 14 days. Simultaneous treatment improved histological damage and increased body weight, colon weight, and colon length, whereas the disease activity index score and collagen deposition were decreased. Simultaneous treatment with treadmill exercise and 5-ASA suppressed pro-inflammatory cytokines and apoptosis following UC. The benefits of this simultaneous treatment may be due to inhibition on nuclear factor-κB/mitogen-activated protein kinase signaling activation. Based on this study, simultaneous treatment of treadmill exercise and 5-ASA can be considered as a new therapy of UC.

The impact of 5-aminosalicylates on the efficacy of mesenchymal stem cell therapy in a murine model of ulcerative colitis.

Inflammatory bowel disease (IBD) is distinguished by persistent immune-mediated inflammation of the gastrointestinal tract. Previous experimental investigations have shown encouraging outcomes for the use of mesenchymal stem cell (MSC)-based therapy in the treatment of IBD. However, as a primary medication for IBD patients, there is limited information regarding the potential interaction between 5-aminosalicylates (5-ASA) and MSCs. In this present study, we employed the dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model to examine the influence of a combination of MSCs and 5-ASA on the development of UC. The mice were subjected to weight measurement, DAI scoring, assessment of calprotectin expression, and collection of colons for histological examination. The findings revealed that both 5-ASA and MSCs have demonstrated efficacy in the treatment of UC. However, it is noteworthy that 5-ASA exhibits a quicker onset of action, while MSCs demonstrate more advantageous and enduring therapeutic effects. Additionally, the combination of 5-ASA and MSC treatment shows a less favorable efficacy compared to the MSCs alone group. Moreover, our study conducted in vitro revealed that 5-ASA could promote MSC migration, but it could also inhibit MSC proliferation, induce apoptosis, overexpress inflammatory factors (IL-2, IL-12P70, and TNF-α), and reduce the expression of PD-L1 and PD-L2. Furthermore, a significant decrease in the viability of MSCs within the colon was observed as a result of 5-ASA induction. These findings collectively indicate that the use of 5-ASA has the potential to interfere with the therapeutic efficacy of MSC transplantation for the treatment of IBD.

Sarcandra glabra (Thunb.) Nakai alleviates DSS-induced ulcerative colitis by promoting restitution, restoring barrier function, and modulating IL-17/Notch1/FoxP3 pathway in intestinal cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Sarcandra glabra is officially named Zhong Jie Feng as a traditional medicine. In the nationality of Yao and Zhuang, it has been used to treat digestive diseases like stomachache and dysentery. Similarly, in Dai nationality, it has been used to treat intestinal diseases like gastric ulcers. However, the effect and mechanism of S. glabra on experimental ulcerative colitis (UC) are known. AIM OF STUDY: The main objective of this study was to investigate the effect and mechanism of S. glabra on experimental UC. MATERIALS AND METHODS: The chemical components in the water extract of S. glabra (ZJF) were analyzed by UPLC-MS/MS method. The HCoEpiC cell line was used to assess the promotive effect on intestinal proliferation and restitution. RAW264.7 cells were used to assess the in vitro anti-inflammatory effect of ZJF. The 3% DSS-induced colitis model was used to evaluate the in vivo effect of ZJF (4.5 g/kg and 9.0 g/kg). Mesalazine (0.5 g/kg) was used as the positive drug. ELISA, RT-qPCR, Western blot, and multiplex immunohistochemical experiments were used to test gene levels in the colon tissue. The H&E staining method was used to monitor the pathological changes of colon tissue. TUNEL assay kit was used to detect apoptosis of epithelial colonic cells. RESULTS: ZJF could alleviate the DSS-caused colitis in colon tissues, showing a comparative effect to that of the positive drug mesalazine. Mechanism study indicated that ZJF could promote normal colonic HCoEpiC cell proliferation and restitution, inhibit overexpression of pro-inflammatory cytokines, restore the M1/M2 ratio, decrease epithelial colonic cell apoptosis, rescue tight junction protein levels, and modulate IL-17/Notch1/FoxP3 pathway to treat experimental UC. CONCLUSION: Our results indicated that S. glabra can promote intestinal cell restitution, balance immune response, and modulate IL-17/Notch1/FoxP3 pathway to treat experimental UC.

The colon targeting efficacies of mesalazine medications and their impacts on the gut microbiome.

Successful treatment of ulcerative colitis (UC) is highly dependent on several parameters, including dosing regimen and the ability to deliver drugs to the disease site. In this study two strategies for delivering mesalazine (5-aminosalicylic acid, 5-ASA) to the colon were compared in an advanced in vitro model of the human gastrointestinal (GI) tract, the SHIME® system. Herein, a prodrug strategy employing bacteria-mediated drug release (sulfasalazine, Azulfidine®) was evaluated alongside a formulation strategy that utilised pH and bacteria-mediated release (5-ASA, Octasa® 1600 mg). SHIME® experiments were performed simulating both the GI physiology and colonic microbiota under healthy and inflammatory bowel disease (IBD) conditions, to study the impact of the disease state and ileal pH variability on colonic 5-ASA delivery. In addition, the effects of the products on the colonic microbiome were investigated by monitoring bacterial growth and metabolites. Results demonstrated that both the prodrug and formulation approaches resulted in a similar percentage of 5-ASA recovery under healthy conditions. On the contrary, during experiments simulating the GI physiology and microbiome of IBD patients (the target population) the formulation strategy resulted in a higher proportion of 5-ASA delivery to the colonic region as compared to the prodrug approach (P < 0.0001). Interestingly, the two products had distinct effects on the synthesis of key bacterial metabolites, such as lactate and short chain fatty acids, which varied according to disease state and ileal pH variability. Further, both 5-ASA and sulfasalazine significantly reduced the growth of the faecal microbiota sourced from six healthy humans. The findings support that the approach selected for colonic drug delivery could significantly influence the effectiveness of UC treatment, and highlight that drugs licensed for UC may differentially impact the growth and functioning of the colonic microbiota.

Early and aggressive treatment for Crohn disease using biologics and immunomodulators.

ABSTRACT: Traditionally, medical providers have used the step-up approach to manage patients with Crohn disease, starting with 5-aminosalicylic acid derivatives, progressing to corticosteroids, and eventually to immunomodulators and biologics. However, a new top-down approach focuses on early and aggressive therapy with biologics and immunomodulators to reduce the rate of mucosal and intestinal damage. This article describes early and aggressive biologic and immunomodulator therapies and new therapeutic parameters compared with traditional step-up treatment for patients with Crohn disease.

Prescribing in pregnant women with inflammatory bowel disease and its relationship to congenital malformations in Japan.

BACKGROUND AND AIM: Inflammatory bowel disease (IBD) frequently affects younger patients and poses various challenges concerning pregnancy and childbirth. Maintaining good disease control throughout pregnancy is crucial, but expectant and pregnant patients may worry about the fetal impact of medications, leading to treatment discontinuation due to uncertainty about this issue. This study investigated the real-world drug-prescribing practices for pregnant patients with IBD in Japan and their potential connection to major congenital malformations (MCMs). METHODS: Overall, 277 female IBD patients who gave birth between 2010 and 2019 were selected from the JMDC claims database. The prescribing patterns of IBD medications and MCMs in the patients' offspring were analyzed. RESULTS: Among pregnant IBD patients, 74.4% received at least one medication from 90 days before pregnancy to 90 days after delivery. Trends in medication prescriptions during pregnancy in 2010-2019 revealed consistent use of oral 5-ASA, variable use of topical medications, a decrease in systemic steroids, and an increase in biologics. The prevalence of MCMs in children born to IBD-affected mothers did not differ significantly between those who did and did not receive IBD medications (8.6% vs 6.8%). Although circulatory system MCMs were slightly more common in the IBD medication group (4.9% vs 1.4%), this difference was not significant. Logistic regression analysis did not reveal an association between MCM risk and first-trimester use of IBD medications, including corticosteroids and biologics. CONCLUSIONS: This study provides insights into medication patterns in pregnant IBD patients and suggests no increased risk of MCMs associated with first-trimester IBD medication use.

Analysis of the Medication Persistence Rate for and Adherence to Oral 5-Aminosalicylic Acid Preparations in Japanese Patients with Ulcerative Colitis: Study Using a Nationwide Claims Database.

INTRODUCTION: 5-aminosalicylic acid (5-ASA) is the first-line drug for the treatment of mild-to-moderate ulcerative colitis (UC). Three oral sustained-release formulations are often used. However, no unified view of their actual use in routine medical practice has been presented to date. METHODS: Using a health insurance claims database, we extracted patients with an initial diagnosis of mild-to-moderate UC during the period from December 1, 2017, to March 31, 2022. For the three types of oral 5-ASA formulation, we calculated and compared descriptive statistics of medication persistence rates (MPR), proportions of days covered (PDC), and adherence proportion (PDC ≥80%) in the extracted population. RESULTS: An oral 5-ASA formulation was used in combination with a topical preparation (cohort 1) in 899 patients, and oral 5-ASA was used alone (cohort 2) in 1,829 patients. In cohort 1, MPR at days 151-180 with concomitant use of topical formulation was significantly higher for the Multi Matrix System™ (MMX) formulation (65.2%) compared with that for pH-dependent formulation (51.7%, p < 0.025), while MPR tended to be higher for MMX than for the time-dependent formulation (56.4%, not significant). During days 151-180 after starting the oral formulation, MPR for MMX (66.7% and 65.8%) was higher than for pH-dependent (55.9% and 55.3%) and time-dependent (57.6% and 55.9%) formulations in cohorts 1 + 2 and 2, respectively. In cohort 1, there was a significant difference between MMX (68.3%) and pH-dependent (57.1%) formulations, but no significant difference was seen with time-dependent formulations (61.8%). In terms of the proportion of adherence until day 180, MMX was significantly better than the other formulations. CONCLUSION: The analyses of the three oral 5-ASA formulations suggested that both MPR and medication adherence were better for the MMX formulation than for time-dependent or pH-dependent formulations.

Huang Qin decoction increases SLC6A4 expression and blocks the NFκB-mediated NLRP3/Caspase1/GSDMD pathway to disrupt colitis-associated carcinogenesis.

Huang Qin decoction (HQD) is a traditional Chinese medicine formula for treating colitis, but the effects and molecular mechanism of action of HQD in colitis-associated carcinogenesis (CAC) are still unclear. Therefore, we aimed to determine the beneficial effects of HQD on CAC in mice and to reveal the underlying mechanism involved. AOM/DSS was used to induce CAC in mice, and the effects of HQD on tumorigenesis in mice were examined (with mesalazine serving as a positive control). Mesalazine or HQD treatment alleviated body weight loss and decreased the disease activity index in mice induced by AOM/DSS. Mesalazine or HQD treatment also suppressed the shortening of colon tissue length, the number of tumors, and the infiltration of inflammatory cells. The genes targeted by HQD were predicted and verified, followed by knockout experiments. Elevated SLC6A4 and inhibited serotonin production and inflammation were observed in HQD-treated mice. HQD inhibited the NFκB and NLRP3/caspase1/GSDMD pathways. The therapeutic effect of HQD was diminished in SLC6A4-deficient AOM/DSS mice. Additionally, the downregulation of SLC6A4 mitigated the inhibitory effect of HQD-containing serum on MODE-K cell pyroptosis. Our findings suggest that SLC6A4 is a pivotal regulator of HQD-alleviated CAC via its modulation of the NLRP3/caspase1/GSDMD pathway.

Anatase and rutile titanium oxide nanoparticles induce acute kidney injury by coadministration with paraquat, cisplatin or 5-aminosalicylic acid.

Nanoparticles are used in a variety of fields; for example, titanium oxide nanoparticles are used in paints, food additives, cosmetics, and sunscreen materials. Although the use of titanium oxide nanoparticles is regulated, their safety has not been established. Furthermore, the interaction between titanium oxide nanoparticles and various chemical substances and pharmaceuticals is unknown. We co-administered rutile-type titanium oxide nanoparticles (nTR) or anatase-type titanium oxide nanoparticles (nTA) to mice together with paraquat (PQ), cisplatin (CDDP), or anti-5-aminosalicylic acid (5-ASA), and investigated the extent, if any, of liver and kidney injury. As a result, when nTA and nTR were administered alone, no increases were observed in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which are indicators of liver damage, or urea nitrogen (BUN), which is an indicator of kidney damage. Next, nTA and nTR were co-administered with PQ, CDDP or 5-ASA. Although no increase in ALT or AST was observed, BUN levels increased significantly and acute kidney injury was induced. The findings suggested that titanium oxide nanoparticles induce acute kidney injury through their interaction with chemicals and drugs.

Synthesis and Bioactive Properties of the Novel Coloured Compound Obtained via the Laccase-Mediated Transformation of 5-Aminosalicylic Acid.

Biocatalysis processes based on oxidoreductases, such as fungal laccase, are important for discovering new organic compounds with broad structures and potential applications. They include bioactive compounds, which can be obtained through laccase-mediated oxidation of organic substrates having hydroxyl and/or amino groups especially, e.g., 5-aminosalicylic acid (5-ASA) is characterised for its potential for oxidation by a fungal laccase obtained from a Cerrena unicolor strain. The biotransformation process was optimised in terms of the buffer and co-solvent concentration, buffer pH value, and laccase activity. Selected crude dyes were analysed for their bioactive properties, toxicity, and suitability for the dyeing of wool fibres. The data obtained clearly indicated that a low concentration of the reaction buffer in the pH range from 5 to 6 and in the presence of 10% acetonitrile increased the rate of substrate oxidation and the amount of the product formed. The red-brown compound obtained via laccase-mediated oxidation of 5-aminosalicylic acid showed antioxidant properties and unique antimicrobial activity against Staphylococcus aureus and Staphylococcus epidermidis strains with the MIC value of 0.125 mg/mL detected for the purest dye. In addition, it was reported to have good wool fibre dyeing properties and no irritant effect after patch tests on a selected group with increased skin sensitivity.

An In Vitro Study Evaluating the Safety of Mesalazine on Human Nasoepithelial Cells.

Chronic rhinosinusitis (CRS) is a disease characterised by the inflammation of the nasal and paranasal cavities. It is a widespread condition with considerable morbidity for patients. Current treatment for chronic rhinosinusitis consists of appropriate medical therapy followed by surgery in medically resistant patients. Although oral steroids are effective, they are associated with significant morbidity, and disease recurrence is common when discontinued. The development of additional steroid sparing therapies is therefore needed. Mesalazine is a commonly used therapeutic in inflammatory bowel disease, which shares a similar disease profile with chronic rhinosinusitis. This exploratory in vitro study aims to investigate whether mesalazine could be repurposed to a nasal wash, which is safe on human nasoepithelial cells, and retains its anti-inflammatory effects. CRS patients' human nasal epithelial cells (HNECs) were collected. HNECs were grown at an air-liquid interface (ALIs) and in a monolayer and challenged with mesalazine or a non-medicated control. Transepithelial electrical resistance, paracellular permeability, and toxicity were measured to assess epithelial integrity and safety. The anti-inflammatory effects of mesalazine on the release of interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) were analysed using human leukemia monocytic cell line (THP-1). mesalazine did not impact the barrier function of HNEC-ALIs and was not toxic when applied to HNECs or THP-1 cells at concentrations up to 20 mM. mesalazine at 0.5 and 1 mM concentrations significantly inhibited TNF-α release by THP-1 cells. mesalazine effectively decreases TNF-α secretion from THP-1 cells, indicating the possibility of its anti-inflammatory properties. The safety profile of mesalazine at doses up to 20 mM suggests that it is safe when applied topically on HNECs.

[Non-distinctive abdominal pain: is it diverticular disease or not?] / Unklare Bauchschmerzen: Wann ist es eine Divertikelkrankheit und wann nicht?

Acute abdominal pain may relate to specific organ systems and needs an interdisciplinary approach with close collaboration between internal and surgical disciplines. Main objective is to shorten the diagnostic work-up between the beginning of the symptoms and their therapy. After clarifying of the five w-questions: when, how, how long, why, and where, abdominal ultrasound, ECG, laboratory diagnostics and early application of computed tomography should be performed.For the most part, chronic abdominal pain is caused by disorders of the gut-brain-axis such as the irritable bowel syndrome. Because of the synaptic plasticity, the processing of pain is dynamic and cannot be related to a single organ system. This problem is obvious in patients with irritable bowel syndrome and colonic diverticula, which may be interpreted as symptomatic uncomplicated diverticular disease (SUDD, type 3a). However, a reliable clinical differentiation between both groups is not possible. The establishment of SUDD (type 3a) considerable widened the application area of mesalazine.

Formulation, Characterization and In Vitro Evaluation of Mesalamine and Bifidobacterium bifidum Loaded Hydrogel Beads in Capsule System for Colon Targeted Delivery.

Mesalamine is a first-line drug for the treatment of inflammatory bowel diseases. However, its premature release associated with marketed formulations leads to adverse effects like gastric trouble, vomiting, and diarrhoea. To minimize these side effects, colon-targeted drug delivery is essential. Besides conventional pharmacotherapy, bifidogenic probiotics with anti-inflammatory activity has been reported to elicit a significant impact on the remission of ulcerative colitis. Bifidogenic probiotics being acid-labile necessitate developing a gastro-resistant formulation for enhancing the delivery of viable cells to the colon. The present study was aimed at developing a fixed-dose unit dosage form of mucoadhesive hydrogel beads loaded with mesalamine and Bifidobacterium bifidum further encapsulated in Eudragit® capsules for the targeted drug delivery at colonic pH. The hydrogel beads were prepared by ionotropic gelation, with the effect of single and dual-crosslinking approaches on various formulation characteristics studied. Standard size 00 Eudragit® gastro-resistant capsules were prepared and the dried beads were filled inside the capsule shells. The formulation was then evaluated for various parameters, including physicochemical characterization, in vitro biocompatibility and anti-inflammatory activity. No interaction was observed between the drug and the polymers, as confirmed through FTIR, XRD, and DSC analysis. The mean particle size of the beads was ~ 457-485 µm. The optimized formulation showed a drug entrapment efficiency of 95.4 ± 2.58%. The Eudragit® capsule shells disintegrated in approximately 13 min at pH 7.4. The mucoadhesive hydrogel beads sustained the drug release above 18 h, with 50% of the drug released by the end of 12 h. The optimized formulation demonstrated significant (p < 0.05) gastro-resistance, biocompatibility, sustained drug release, cell viability, and anti-inflammatory activity.