Diabetic wounds (DWs) are considered chronic complications observed in patients suffering from type 2 diabetes mellitus (DM). Usually, DWs originate from the interplay of inflammation, oxidation, impaired tissue re-epithelialization, vasculopathy, nephropathy, and neuropathy, all of which are related to insulin resistance and sensitivity. The conventional approaches available for the treatment of DWs are mainly confined to the relief of wound pressure, debridement of the wound, and management of infection. In this paper, we speculate that treatment of DWs with 5-aminosalicylic acid (5-ASA) and subsequent activation of peroxisome proliferator-activated receptor gamma (PPAR-γ) and transforming growth factor beta (TGF-β) via the AhR pathway might be highly beneficial for DW patients. This estimation is based on several lines of evidence showing that 5-ASA and PPAR-γ activation are involved in the restoration of insulin sensitivity, re-epithelialization, and microcirculation. Additionally, 5-ASA and TGF-β activate inflammation and the production of pro-inflammatory mediators. Suitable stabilized formulations of 5-ASA with high absorption rates are indispensable for scrutinizing its probable pharmacological benefits since 5-ASA is known to possess lower solubility profiles because of its reduced permeability through skin tissue. In vitro and in vivo studies with stabilized formulations and a control (placebo) are mandatory to determine whether 5-ASA indeed holds promise for the curative treatment of DWs.

UNASSIGNED: Intestinal mucosal immune cells, notably mast cells, are pivotal in ulcerative colitis (UC) pathophysiology. Its activation elevates tissue concentrations of histamine. Inhibiting colonic histamine release could be an effective therapeutic strategy for treating UC. Experimental model like 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats mimic human IBD, aiding treatment investigations. Drug repurposing is a promising strategy to explore new indications for established drugs. Desloratadine (DES) is second-generation antihistamine utilized for managing allergies by blocking histamine action in the body. It also has reported anti-inflammatory and antioxidant actions.
UNASSIGNED: DES was investigated for its repurposing potential in UC by preclinical screening in TNBS-induced colitis in Wistar rats.
UNASSIGNED: Therapeutic efficacy of DES was evaluated both individually and in combination with standard drug 5-aminosalicylicacid (5-ASA). Rats were orally administered DES (10 mg/kg), 5-ASA (25 mg/kg), and DES + 5-ASA (5 mg + 12.15 mg) following the induction of colitis. Parameters including disease activity score rate (DASR), colon/body weight ratio (CBWR), colon length, diameter, pH, histological injury, and scoring were evaluated. Inflammatory biomarkers such as IL-1β, TNF-α, along with reduced glutathione (GSH), and malondialdehyde (MDA) were assessed.
UNASSIGNED: Significant protective effects of DES, especially in combination with 5-ASA, against TNBS-induced inflammation were observed as evidenced by reduced DASR, CBWR, and improved colon morphology. Drugs significantly lowered plasma and colon histamine and, cytokines levels. GSH restoration, and decreased MDA content were also observed.
UNASSIGNED: DES and DES + 5-ASA demonstrated potential in alleviating colonic inflammation associated with TNBS-induced colitis in rats. The effect can be attributed to its antihistamine, anticytokine, and antioxidative properties.

UNASSIGNED: Given the widespread use of Chinese patent medicines (CPMs) in combination with 5-aminosalicylic acid (5-ASA) for Ulcerative colitis (UC) patients, this study aimed to evaluate the efficacy and safety of nine CPMs combined with 5-ASA in the treatment of UC.
UNASSIGNED: A systematic literature search was conducted in eight databases from inception to May 2023 to identify eligible RCTs evaluating the effects of CPM combined with 5-ASA for the treatment of UC. The methodological quality of the included RCTs was assessed using the Cochrane risk of bias tool in Review Manager 5.4. The primary outcome of the meta-analysis was the overall response rate. The secondary outcomes included excellent rate, disease activity index (DAI), IL-6, IL-8, and TNF-α levels, mean platelet volume (MPV), fibrinogen (FIB) levels, recurrence rate, and adverse event rate. Network meta-analysis was performed using Review Manager 5.4 and Stata 15.0.
UNASSIGNED: In total, 70 RCTs including 5973 patients and 10 treatment regimens were included. The combination of Kangfuxin Liquid (KFL) and 5-ASA showed the greatest efficacy in improving FIB levels and the overall response rate. Bupi Yichang Pill (BYP) combined with 5-ASA was associated with the fewest adverse events and the lowest recurrence rate. Hudi Enteric-coated Capsule (HEC) combined with 5-ASA ranked first in improving DAI. ZhiKang Capsule (ZKC), ChangYanNing Capsule (CYN), and Danshen Injection (DSI) combined with 5-ASA ranked first in improving IL-6, IL-10, and TNF-α levels, respectively. Shenling Baizhu Powder (SBP) combined with 5-ASA was associated with the highest excellent rate.
UNASSIGNED: CPM combined with 5-ASA may be more effective than 5-ASA alone for treating UC. Besides, CPM combined with 5-ASA could better reduce the recurrence rate and adverse event rate in UC patients. The current meta-analysis provides statistical evidence for clinical application.Systematic Review Registration: International Prospective Register of Systematic Reviews (PROSPERO), No. CRD42023433672.

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.

The oral formulation design for colon-specific drug delivery brings some therapeutic benefits in the ulcerative colitis treatment. We recently reported the specific delivery of hemoglobin nanoparticles-conjugating 5-aminosalicylic acid (5-ASA-HbNPs) to the inflamed site. In the current study, the therapeutic effect of the 5-ASA-HbNPs formulation was confirmed in vivo. This evaluation of 5-ASA-HbNPs not only shows longer colonic retention time due to adhesive properties, also provides full support for it as compared with free 5-ASA. It was considered as a suitable bio-adhesive nanoparticle with mucoadhesive property to pass through the mucus layer and accumulate into the mucosa. In UC model mice, a two-fold decrease in the disease activity indexes and colon weight/length ratios was significantly observed in the group treated with 5-ASA-HbNPs. This group received one percent of the standard dosage of 5-ASA (50 μg/kg), while, a similar result was observed for a significant amount of free 5-ASA (5 mg/kg). Furthermore, microscopic images of histological sections of the extracted colons demonstrated that the 5-ASA-HbNPs and 5-ASA groups displayed instances of inflammatory damage within the colon. However, in comparison to the colitis group, the extent of this damage was relatively moderate, suggesting 5-ASA-HbNPs improved therapeutic efficacy with the lower dosage form.

UNASSIGNED: Drug-induced liver injury (DILI) associated with 5-aminosalicylic acid (5-ASA) is a rare but potentially life-threatening adverse event.
UNASSIGNED: We report the case of a 58-year-old woman with ulcerative colitis who developed DILI after initiating maintenance therapy with the multimatrix system 5-ASA. The patient presented with grade 4 liver enzyme elevation on day 98 after initiating 5-ASA and was admitted to the hospital. Blood tests revealed the mixed liver injury, and imaging studies showed no abnormalities except for mild lymph node enlargement. Liver biopsy revealed acute lobular hepatitis with interfacial activity. The patient\'s score on the International Autoimmune Hepatitis Group 1999 revised scoring system was a total score of 10, causing a suspicion for the diagnosis of autoimmune hepatitis. The DDW-J 2004 scale calculated a total score of six, indicating a high probability of DILI. We suspected DILI due to 5-ASA, and the 5-ASA formulations were discontinued. The patient was treated with ursodeoxycholic acid and neominophagen C, and her liver function gradually improved without steroid treatment. Finally, we definitively diagnosed DILI based on the pathological findings and clinical course after discontinuation of 5-ASA.
UNASSIGNED: This case highlights the importance of monitoring liver function in patients receiving 5-ASA therapy.

UNASSIGNED: There are conflicting data as to whether co-treatment with 5-aminosalicylic acid (5-ASA) in patients with inflammatory bowel disease (IBD) under azathioprine (AZA) or 6-mercaptopurine (6-MP) therapy may influence 6-thioguanine nucleotide (6-TGN) concentrations, and whether this combination puts patients at risk of side-effects. The aim of the study was to determine 6-TGN levels in patients treated with AZA/6-MP, either alone or in combination with 5-ASA.
UNASSIGNED: Available blood samples from patients treated with AZA or 6-MP were retrieved from the Swiss IBD Cohort Study (SIBDCS). The eligible individuals were divided into 2 groups: those with vs. without 5-ASA co-medication. Levels of 6-TGN and 6-methylmercaptopurine ribonucleotides (6-MMPR) were determined and compared. Potential confounders were compared between the groups, and also evaluated as potential predictors for a multivariate regression model.
UNASSIGNED: Of the 110 patients enrolled in this analysis, 40 received concomitant 5-ASA at the time of blood sampling. The median 6-TGN levels in patients with vs. those without 5-ASA co-treatment were 261 and 257 pmol/8×108 erythrocytes, respectively (P=0.97). Likewise, there were no significant differences in 6-MMPR levels (P=0.79). Through multivariate analysis, 6-TGN levels were found to be significantly higher in non-smokers, patients without prior surgery, and those without signs of stress-hyperarousal.
UNASSIGNED: Blood concentrations of 6-TGN and 6-MMPR did not differ between patients with vs. those without 5-ASA co-treatment. Our data warrant neither more frequent lab monitoring nor dose adaptation of AZA in patients receiving concomitant 5-ASA treatment.

Two 8-week, randomized, placebo-controlled parent studies, SPD476-301 (by Lichtenstein and associates) and SPD476-302 (by Kamm and colleagues), of MMX Multi Matrix System (MMX) mesalamine have evaluated the induction of remission in ulcerative colitis patients, and a third study has evaluated the maintenance of remission in patients from these parent studies. Here, we examine data only from patients who received MMX mesalamine 2.4 g or 4.8 g daily in these trials. In total, 63.6% of patients (220/346) achieved remission following 8-16 weeks of MMX mesalamine therapy. Among these 220 eligible patients, 218 entered the 12-month maintenance phase, and of this group, 89.9% (196/218) were relapse-free at study end. Overall, 56.6% (196/346) of patients who started MMX mesalamine therapy both achieved and maintained remission for 12 months. The adverse-event profile of MMX mesalamine was similar to the profile of the parent studies\' placebo arms at all doses and frequencies. Therefore, the majority of patients with active, mild-to-moderate ulcerative colitis can achieve remission, including complete symptom resolution and mucosal healing, and remain relapse-free for at least 1 year with MMX mesalamine.

Eudragit S100-coated bile salt-containing liposomes were prepared and optimized by experimenting with different variables, including bile salt type and concentration, and the method of incorporation into liposomes using a model hydrophilic compound, 5-aminosalicylic acid (5-ASA). After optimizing the formulation, cellular uptake, and animal pharmacokinetic experiments were performed. The inclusion of sodium glycocholate (SG) into liposomes decreased liposome particle size and entrapment efficiency significantly but had no effect on zeta potential. The method of incorporating SG into the lipid or aqueous phase of the liposome did not notably impact the characteristics of the liposomes but the hydration media had a substantial effect on the entrapment efficiency of 5-ASA. In vitro drug release in different fluids simulating distinct gastrointestinal tract sections, indicated pH-dependent disintegration of the coating layer of coated SG-containing liposomes. The majority of the drug was retained when subjected to simulated gastric fluid (SGF) and fed-state simulated intestinal fluid (FeSSIF) (≈ 37% release after 2 h in SGF pH 1.2, followed by 3 h in FeSSIF pH 5). The remaining drug was subsequently released in phosphate-buffered saline pH 7.4 (≈ 85% release within 24 h). Increasing SG concentration in the liposomes decreased the amount of drug released in FeSSIF. Similar results were observed when SG was replaced with sodium taurocholate. Cellular uptake studies in Caco-2 cells demonstrated that all liposomal formulations (conventional liposomes, bile salt-containing liposomes, and coated bile salt-containing liposomes) have shown to be equally effective at increasing the cellular uptake compared to free fluorescein solution. In the pharmacokinetic study, coated bile salt-containing liposomes showed a lower Cmax and prolonged residence in the gastrointestinal tract in comparison to conventional liposomes. Taken together, these findings suggest that the polymer-coated bile salt-containing liposomes have the potential to serve as a drug delivery system targeted at the colon.

Dual-nozzle fused deposition modeling (FDM) is a 3D printing technique that allows for the simultaneous printing of two polymeric filaments and the design of complex geometries. Hence, hybrid formulations and structurally different sections can be combined into the same dosage form to achieve customized drug release kinetics. The objective of this study was to develop a novel bicompartmental device by dual-nozzle FDM for colon-specific drug delivery. Hydroxypropylmethylcellulose acetate succinate (HPMCAS) and polyvinyl alcohol (PVA) were selected as matrix-forming polymers of the outer pH-dependent and the inner water-soluble compartments, respectively. 5-Aminosalicylic acid (5-ASA) was selected as the model drug. Drug-free HPMCAS and drug-loaded PVA filaments suitable for FDM were extruded, and their properties were assessed by thermal, X-ray diffraction, microscopy, and texture analysis techniques. 5-ASA (20% w/w) remained mostly crystalline in the PVA matrix. Filaments were successfully printed into bicompartmental devices combining an outer cylindrical compartment and an inner spiral-shaped compartment that communicates with the external media through an opening. Scanning electron microscopy and X-ray tomography analysis were performed to guarantee the quality of the 3D-printed devices. In vitro drug release tests demonstrated a pH-responsive biphasic release pattern: a slow and sustained release period (pH values of 1.2 and 6.8) controlled by drug diffusion followed by a faster drug release phase (pH 7.4) governed by polymer relaxation/erosion. Overall, this research demonstrates the feasibility of the dual-nozzle FDM technique to obtain an innovative 3D-printed bicompartmental device for targeting 5-ASA to the colon.