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The present study was carried out to evaluate the effects of olsalazine pretreatment in the potentiation of chemosensitivity of gemcitabine for the treatment of hepatocellular carcinoma (HCC). In silico molecular docking was performed to analyze the interactions of olsalazine and gemcitabine with DNMT1 and DNA, respectively, using the AutoDock tools 1.5.6. Cytotoxicity of olsalazine, gemcitabine, and combination was measured on human HePG2 cells using MTT assay. Anti‐tumor effects of the combination were assessed using animal model of N‐nitrosodiethylamine and carbon tetrachloride‐induced HCC. Treatment was initiated from 8th week of induction to 11th week and changes in body weight, liver weight (absolute and relative), and survival rate were measured. Following treatment, blood samples were collected for estimation of serum biochemistry. Blood serum was used for the estimation of inflammatory cytokines: tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), C‐reactive protein [CRP], lactate dehydrogenase (LDH), and P53 levels. Oxidative stress markers were measured in liver tissue homogenates. Histopathology and immunohistochemistry (IHC) were performed on liver sections to detect the morphological changes and P53 expression. Docking analysis revealed the interactions between olsalazine and DNMT1 with a binding energy score of −5.34 and gemcitabine and DNA with a binding energy score of −5.93. Olsalazine pretreatment potentiated the anticancer effects of gemcitabine in cell line study. In the groups receiving olsalazine pretreatment showed significant reductions in relative liver weight and improved survival rate. Serum biochemical markers: serum glutamate pyruvate transaminase, serum glutamic oxaloacetic transaminase, alkaline phosphatase, and bilirubin revealed improved liver functions. Olsalazine pretreatment also reduced the levels of inflammatory markers: CRP, LDH, TNF‐α, and IL‐6 and oxidative stress markers dose dependently. Histopathology and IHC showed improved liver morphology with potentiated induction of P53 upon olsalazine pretreatment in combination with gemcitabine. In conclusion, sequential combination of olsalazine and gemcitabine improved the treatment outcomes during the progression of HCC. [ABSTRACT FROM AUTHOR]

A procedure was developed for preparing [99mTc]-tricarbonyl-5-[(3-carboxy-4-hydroxyphenyl)diazenyl]-2-hydroxybenzoic acid complex ([99mTc]-tricarbonyl-Olsalazine), for ulcerative colitis (UC) imaging. High yield and 98.5% radiochemical purity of [99mTc]-tricarbonyl-Olsalazine were reached under optimized conditions. Thin layer chromatography (TLC) was used for the purification of the labeled compound. Reversed-phase high-performance liquid chromatography (RP-HPLC) was also used. A biodistribution study performed with a microbial mouse model of UC showed that the colon localization of [99mTc]-tricarbonyl-Olsalazine was the highest (77 ± 1.7% ID/g) at 120 min post injection. The agent was still present in the ulcerated colon for up to 24 h post injection (75% ID/g). Such level was not reached in previous studies. Thus, [99mTc]-tricarbonyl-Olsalazine can be used as a radiotracer for UC imaging in mice. [ABSTRACT FROM AUTHOR]

Despite the extensive explorations of nanoscale metal−organic frameworks (nanoMOFs) in drug delivery, the intrinsic bioactivity of nanoMOFs, such as anticancer activity, is severely underestimated owing to the overlooked integration of the hierarchical components including nanosized MOFs and molecular-level organic ligands and metal-organic complexes. Herein, we propose a de novo design of multifunctional bioactive nanoMOFs ranging from molecular to nanoscale level, and demonstrate this proof-of-concept by a copper−olsalazine (Olsa, a clinically approved drug for inflammatory bowel disease, here as a bioactive linker and DNA hypomethylating agent) nanoMOF displaying a multifaceted anticancer mechanism: (1) Cu-Olsa nanoMOF-mediated redox dyshomeostasis for enhanced catalytic tumor therapy, (2) targeting downregulation of cyclooxygenase-2 by the organic complex of Cu2+ and Olsa, and (3) Olsa-mediated epigenetic regulation. Cu-Olsa nanoMOF displayed an enzyme-like catalytic activity to generate cancericidal species ·OH and 1O 2 from rich H 2 O 2 in tumors, improved the expression of tumor suppressors TIMP3 and AXIN2 by epigenetic modulation, and fulfilled selective inhibition of colorectal cancer cells over normal cells. The hyaluronic acid-modified nanoMOF further verified the efficient suppression of CT26 colorectal tumor growth and metastasis in murine models. Overall, these results suggest that Olsa-based MOF presents a platform of epigenetic therapy-synergized nanomedicine for efficient cancer treatment and provides a powerful strategy for the design of intrinsically bioactive nanoMOFs. Metal−organic frameworks (MOFs) with intrinsic bioactivities such as anticancer and antibacterial activity are of great interest. Herein, we reported a bioactive copper−olsalazine (Cu-Olsa) nanoMOF as a nanodrug for colorectal cancer treatment. This nanoMOF per se displayed enzyme-like catalytic activity to generate cancericidal species ·OH and 1O 2 from rich H 2 O 2 in tumors for nanocatalytic tumor therapy. Upon dissociation into small molecular copper-organic complex and olsalazine in cancer cells, COX-2 inhibition and epigenetic modulation were fulfilled for selective inhibition of colorectal cancer growth and metastasis. [Display omitted] [ABSTRACT FROM AUTHOR]

Because of its anti‐inflammatory properties, 5‐aminosalicylic acid (5‐ASA) is used in medicines for intestinal diseases such as: Crohn′s disease and ulcerative colitis. This compound is contained in unchanged form in enteric‐coated tablets to prevent early absorption and subsequent metabolism. Another strategy is pursued with the prodrug concept: For this, 5‐ASA is converted into azosalicylic acid, a stable compound without its own biological activity. This compound is then broken down into active 5‐ASA molecules in the intestine by bacterial azoreductases. The present article takes a look at the interesting development history of azosalicylic acid. Afterwards, extensive suggestions (concept, experiments, models) are given for implementing this interdisciplinary topic in chemistry lessons of secondary level. [ABSTRACT FROM AUTHOR]

Background and purpose: Since DNA methyltransferase enzymes play a key role in DNA methylation, they can be used as a target to alter epigenetic changes and treat cancer. Recent studies have shown that olsalazine, through its potent inhibitory effect on the DNA methyltransferase enzyme, can be a good option. The aim of this study was to investigate the effects of olsalazine on cell viability and expression of CDH1 and uPA genes in MDA-MB-231 cells compared with decitabine. Experimental approach: The cytotoxicity of the drugs was determined using a standard MTT assay. MDA-MB-231 cells were treated with olsalazine and decitabine with concentrations less than IC50 to evaluate the effect of drugs on the expression of genes. RNA was extracted from the cells after 24 and 48 h and CDH1and uPA gene expression were evaluated by quantitative real-time polymerase chain reaction method. Findings/Results: The cytotoxicity of the two drugs was comparable. The IC50 values at 24 h were 4000 and 4500 μM for olsalazine and decitabine, respectively. The IC50 values of both drugs were about 300 μM at 48 h. Statistical analyzes showed a significant increase in CDH1 expression after 24-48 h treatment with olsalazine, and 48 h treatment with decitabine, without any significant increase in uPA expression. Conclusion and implications: Our results showed that olsalazine has cellular toxicity comparable to decitabine in MDA-MB-231 cells. Also compared to decitabine, olsalazine causes a greater increase in expression of CDH1 without any significant increase in uPA expression. Therefore, it appears to be a good candidate for cancer treatment.

Fixed-dose combinations have shown to be a great alternative to traditional polytherapy; however, development of such formulation requires thorough physicochemical compatibility investigation of active pharmaceutical ingredients to provide a stable, safe and therapeutically effective product. In this work, differential scanning calorimetry, X-ray powder diffraction, isothermal stress testing followed by Fouriertransform infrared spectroscopy and chromatographic analysis as well as dissolution studies were used for physicochemical compatibility investigation of folic acid and balsalazide or olsalazine. Balsalazide and olsalazine as well as their blend were successfully characterised regarding their physicochemical properties using the mentioned techniques. Differential scanning calorimetry gave ambiguous results due to premature degradation of balsalazide. On the contrary, other techniques have implied the absence of any chemical reactions or physical changes in prepared blends. Obtained result imply that folic acid is compatible with both balsalazide and olsalazine which goes in favour of developing proposed fixed-dose combinations. [ABSTRACT FROM AUTHOR]

We report the detection and quantification of important ulcerative colitis drugs olsalazine (OLS) and sulfasalazine (SUL) by the spectrofluorometric method. The proposed method was optimized and validated by using the quenching effect on the acriflavine fluorescence. The method was applied on the detection and quantification of OLS and SUL under optimized conditions showing the calibration curves were linear (range: 1.0–10.0 µg ml−1), with correlation coefficients R2 of 0.9999 for both drugs. The limits of detection (LOD) and quantification (LOQ) were 53 and 104 ng ml−1 for the OLS and 160 and 315 ng ml−1 for the SUL. This method permitted the analysis of OLS and SUL in their pure and pharmaceutical forms. The proposed spectrofluorimetric method was also evaluated against ‘green’ criteria and all the experimental results make it an eco-friendly and safe method for the detection of OLS and SUL.

The indiscriminate disposal of olsalazine in the environment poses a threat to human health and natural ecosystems because of its cytotoxic and genotoxic nature. In the present study, degradation efficiency of olsalazine by the marine-derived fungus, Aspergillus aculeatus (MT492456) was investigated. Optimization of physicochemical parameters (pH. Temperature, Dry weight) and redox mediators {(2,20-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), p-Coumaric acid and 1-hydroxybenzotriazole (HOBT)} was achieved with Response Surface Methodology (RSM)-Box-Behnken Design (BBD) resulting in 89.43% removal of olsalazine on 7th day. The second-order polynomial regression model was found to be statistically significant, adequate and fit with p

Olsalazine (Olsa) is a broad‐spectrum anti‐cancer agent acting as a DNA‐methylation inhibitor. When conjugated to 2‐cyano‐6‐aminobenzothiazole and a peptide substrate specific for the tumor‐overexpressed enzyme furin, it can self‐assemble into nanoparticles that can be detected by chemical‐exchange saturation‐transfer magnetic‐resonance imaging (CEST MRI). We report here that these nano‐assemblies can also be detected with high specificity in furin‐overexpressing tumor cells by Raman spectroscopy with a distinct scattering signature and demonstrate the utility of this sensing mechanism in vitro and in vivo. Our findings suggest that Raman spectroscopy could be used for high‐resolution image‐guided surgery to precisely delineate tumor margins during and after resection in real‐time as well as to determine microscopic tumor invasion and multifocal locoregional tumor spread, which are currently impossible to visualize with available imaging technologies, including CEST MRI. [ABSTRACT FROM AUTHOR]

• An acryloyl chloride modified olsalazine (olsalazine-AC) as an azo crosslinker was synthesized. • Two types of azo hydrogels which contained single network hydrogel and interpenetrating network hydrogel were synthesized. • The results showed that these azo hydrogels could be potential drug carrier for colon-targeted delivery. Colon-specific drug delivery systems are efficient for increasing the availability of drugs at colon region and are desirable for the treatment of local diseases such as ulcerative colitis and colonic cancer. We synthesized an acryloyl chloride modified olsalazine (olsalazine-AC) as an azo crosslinker which was copolymerized with hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA), and developed two types of azo hydrogels which contained single network hydrogel and interpenetrating network hydrogel as an enzyme responsive and pH responsive controlled release carrier for colon-specific drug delivery. The structure of the azo crosslinker was characterized by FT-IR and 1H NMR spectra and the azo hydrogels were analyzed by using ultraviolet spectrophotometer and scanning electron microscopy. The in vitro release of the 5-flurouracil (5-FU) loaded azo hydrogels was carried out in PBS (pH 7.4), PBS (pH 2.0) and rat colonic fluid (RCF). The drug release profile revealed that 5-FU loaded in azo hydrogels released faster in rat colonic fluid. The results showed that these azo hydrogels could be potential drug carrier for colon-targeted delivery. [ABSTRACT FROM AUTHOR]

Abstract In this work, the supramolecular host-guest interaction of the prodrug Olsalazine (OLZ) and β-Cyclodextrin (β-CD) was examined experimentally and computationally. Experimentally, employing the UV–Vis spectroscopic method in aqueous media at various pH's, results obtained using the Benesi-Hilderbrand approach demonstrated that OLZ can form supramolecular inclusion complex with β-CD with stoichiometric ratio of 1:1. Furthermore, these results revealed that the formation of OLZ: β-CD complexes exhibited insignificant pH dependency in the range 5–8 with an average binding constant (K b) of approximately 1 × 103 M−1. Computationally, geometry optimization of 1:1 OLZ: β-CD complexes was performed employing the ONIOM (DFT((ωB97XB)/6–31 + G(d)),SQM(PM3)) approach. Obtained results demonstrated that OLZ: β-CD complex is stabilized by the formation of intermolecular hydrogen bonds with an average length of approximately 1.8 Å. Additionally, the stability of OLZ: β-CD complex was demonstrated employing ADMP molecular dynamic simulations over a timeframe of 500 fs. The molecularity of the supramolecular host-guest interaction between OLZ and β-CD is presented and interpreted in the essence of TD-DFT and molecular orbitals analyses. Graphical Abstract Unlabelled Image Highlights • Olsalazine:β-CD supramolecular system was examined experimentally and computationally. • Olsalazine can form 1:1 supramolecular inclusion complexes with β-CD. • Olsalazine:β-CD complexes are stabilized by strong hydrogen bonding. • ADMP molecular dynamics simulations demonstrated the stability of Olsalazine:β-CD. • Molecularity of supramolecular interaction is interpreted in terms of molecular orbitals analyses. [ABSTRACT FROM AUTHOR]

A greener protocol for the synthesis of olsalazine analogs is reported. Olsalazine analogs are prepared in high yields by a one-pot reaction of two molecules of mesalazine with benzotriazole-activated aspartic acid and glutamic acid in water under microwave irradiation.

Inflammatory bowel disease (IBD) is a chronic and refractory condition characterized by disrupted epithelial barrier, dysregulated immune balance, and altered gut microbiota. Nano-enabled interventions for restoring gut homeostasis have the potential to alleviate inflammation in IBD. Herein, we developed a combination of olsalazine (Olsa)-based nanoneedles and microbiota-regulating inulin gel to reshape intestinal homeostasis and relieve inflammation. The Olsa-derived nanoneedles exhibited reactive oxygen species scavenging ability and anti-inflammatory effects in lipopolysaccharide-simulated macrophages. The composite of nanoneedles and inulin gel (Cu 2 (Olsa)/Gel) displayed a macroporous structure, improved bio-adhesion, and enhanced colon retention after oral administration. Mechanistically, the composite effectively downregulated pro-inflammatory cytokine levels and promoted epithelial barrier repair through anti-inflammatory and antioxidant therapies, resulting in significant alleviation of colitis in three animal models of IBD. Furthermore, analysis of gut microbiota revealed that Cu 2 (Olsa)/Gel treatment increased the diversity of intestinal microflora and decreased the relative abundance of pathogenic bacteria such as Proteobacteria . Overall, this study provides a self-delivering nanodrug and dietary fiber hydrogel composite for IBD therapy, offering an efficient approach to restore intestinal homeostasis., (© 2023 The Authors.)

Improving the activity and selectivity profile of anticancer agents will require designing drug carrier systems that employ soluble macromolecules. Olsalazine-PAMAM-dendrimer-salicylic acid-conjugates with dendritic arms of different lengths have shown good stability regarding the chemical link between drug and spacer. In this study, the drug release was followed in vitro by ultraviolet (UV) studies. Evaluation of the cytotoxicity of the olsalazine-PAMAM-dendrimer-salicylic acid-conjugates employing a sulforhodamine B (SRB) assay in PC-3 (human prostatic adenocarcinoma) and MCF-7 (human mammary adenocarcinoma) cell lines demonstrated that conjugate 9 was more active as an antiproliferative agent than cisplatin, and no cytotoxicity towards the African green monkey kidney fibroblast (COS-7) cell line was observed in any of the conjugates synthesized in the present work.

Purpose Evaluate ex vivo the bacterial metabolism induced degradation rates of mesalamine (negative control), metronidazole and olsalazine in distal ileum and in cecum. Methods The contents of distal ileum and cecum were collected during colonoscopy under anaerobic conditions from twelve healthy adults in the fasted and in the fed state. To eliminate potential effects of enzymes that may exist in the fluid of lower intestine, each sample was ultracentrifuged and the precipitate was diluted with a volume of normal saline equivalent to that of the supernatant, after ultracentrifugation of intestinal contents from which the specific precipitate had been obtained. Degradation of the three model drugs in individual materials was evaluated anaerobically. Results Mesalamine was stable in all cases. Degradation rates of metronidazole and olsalazine were higher in cecum than in distal ileum, only in the fasted state; no trend could be observed in the fed state. Degradation rates of metronidazole and olsalazine were decreased in the fed state in the cecum; no trend could be observed in distal ileum. Conclusions In the fasted state, bacterial activity is higher in cecum than in distal ileum. Food residues decrease bacterial metabolism degradation rates of drugs in cecum. [ABSTRACT FROM AUTHOR]

GPR35, a class A G-protein-coupled receptor, is considered an orphan receptor; the endogenous ligand and precise physiological function of GPR35 remain obscure. GPR35 is expressed relatively highly in the gastrointestinal tract and immune cells. It plays a role in colorectal diseases like inflammatory bowel diseases (IBDs) and colon cancer. More recently, the development of GPR35 targeting anti-IBD drugs is in solid request. Nevertheless, the development process is in stagnation due to the lack of a highly potent GPR35 agonist that is also active comparably in both human and mouse orthologs. Therefore, we proposed to find compounds for GPR35 agonist development, especially for the human ortholog of GPR35. As an efficient way to pick up a safe and effective GPR35 targeting anti-IBD drug, we screened Food and Drug Administration (FDA)-approved 1850 drugs using a two-step DMR assay. Interestingly, we found aminosalicylates, first-line medicine for IBDs whose precise target remains unknown, exhibited activity on both human and mouse GPR35. Among these, pro-drug olsalazine showed the most potency on GPR35 agonism, inducing ERK phosphorylation and β-arrestin2 translocation. In dextran sodium sulfate (DSS)-induced colitis, the protective effect on disease progression and inhibitory effect on TNFα mRNA expression, NF-κB and JAK-STAT3 pathway of olsalazine are compromised in GPR35 knock-out mice. The present study identified a target for first-line medicine aminosalicylates, highlighted that uncleaved pro-drug olsalazine is effective, and provided a new concept for the design of aminosalicylic GPR35 targeting anti-IBD drug. [ABSTRACT FROM AUTHOR]

Fecal material prepared from human stools is frequently used for the assessment of bacterial degradation of active pharmaceutical ingredients as relevant data are useful for evaluating the potential for colonic drug delivery. The impact of handling and storage of human fecal material on bacterial activity was assessed by evaluating the degradation characteristics of metronidazole and olsalazine. Multiple freeze (−70°C)–thaw cycles should be avoided. Incubation of frozen material for about 2 h in the anaerobic workstation ensures regeneration of the highest possible bacterial activity. Material could be stored at −70°C for at least 12 months. [ABSTRACT FROM AUTHOR]

Colon-targeted drug delivery and circumventing drug resistance are extremely important for colon cancer chemotherapy. Our previous work found that dimethyl fumarate (DMF), the approved drug by the FDA for the treatment of multiple sclerosis, exhibited anti-tumor activity on colon cancer cells. Based on the pharmacological properties of DMF and azo bond in olsalazine chemical structure, we designed azo polymeric micelles for colon-targeted dimethyl fumarate delivery for colon cancer therapy. We synthesized the star-shape amphiphilic polymer with azo bond and fabricated the DMF-loaded azo polymeric micelles. The four-arm polymer star-PCL-azo-mPEG (sPCEG-azo) (constituted by star-shape PCL (polycaprolactone) and mPEG (methoxypolyethylene glycols)-olsalazine) showed self-assembly ability. The average diameter and polydispersity index of the DMF-loaded sPCEG-azo polymeric micelles were 153.6 nm and 0.195, respectively. In vitro drug release study showed that the cumulative release of DMF from the DMF-loaded sPCEG-azo polymeric micelles was no more than 20% in rat gastric fluid within 10 h, whereas in the rat colonic fluids, the cumulative release of DMF reached 60% in the initial 2 h and 100% within 10 h, indicating that the DMF-loaded sPCEG-azo polymeric micelles had excellent colon-targeted property. The DMF-loaded sPCEG-azo polymeric micelles had no significant cytotoxicity on colon cancer cells in phosphate buffered solution (PBS) and rat gastric fluid. In rat colonic fluid, the micelles showed significant cytotoxic effect on colon cancer cells. The blank sPCEG-azo polymeric micelles (without DMF) showed no cytotoxic effect on colon cancer cells in rat colonic fluids. In conclusion, the DMF-loaded sPCEG-azo polymeric micelles show colon-targeted DMF release and anti-tumor activity, providing a novel approach potential for colon cancer therapy. Statement of Significance Colon-targeted drug delivery and circumventing drug resistance are extremely important for colon cancer chemotherapy. Our previous work found that dimethyl fumarate (DMF), the approved drug by the FDA for the treatment of multiple sclerosis, exhibited anti-tumor activities on colon cancer cells ( Br J Pharmacol . 2015 172 ( 15 ): 3929-43 .). Based on the pharmacological properties of DMF and azo bond in olsalazine chemical structure, we designed azo polymeric micelles for colon-targeted dimethyl fumarate delivery for colon cancer therapy. We found that the DMF-loaded sPCEG-azo polymeric micelles showed colon-targeted DMF release and anti-tumor activities, providing a novel approach potential for colon cancer therapy. [ABSTRACT FROM AUTHOR]

A greener protocol for the synthesis of olsalazine analogs is reported. Olsalazine analogs are prepared in high yields by a one-pot reaction of two molecules of mesalazine with benzotriazole-activated aspartic acid and glutamic acid in water under microwave irradiation. A greener protocol for the synthesis of olsalazine analogs is reported. Olsalazine analogs are prepared in high yields by a one-pot reaction of two molecules of mesalazine and aspartic/glutamic benzotriazoles in water under microwave irradiation. [ABSTRACT FROM PUBLISHER]

Ulcerative colitis is a chronic disease having a regressive nature. Commonly used diagnostic methods have the disadvantage to be invasive, time-consuming, and expensive. Therefore, a new sensitive method for the detection and monitoring of disease activity is urgently needed in clinical practice. In the current investigation, radio complexation of olsalazine with technetium-99m, its characterization, and optimization of the labeling conditions were explored. Optimum radiochemical yield of 99mTc-olsalazine (97.6% ± 1.8%) was obtained via direct complexation with technetium-99m (~200 MBq) in the presence of stannous chloride dihydrate (100 µg) as reducing agent at pH 6. It was observed that the complex showed significant in vitro stability in serum at 37°C for more than 11 h. The computer-generated optimized geometries of the 99mTc-olsalazine were reported, and biodistribution studies were carried out using chemically and microbiologically mice-induced ulcerative colitis models. The tracer showed a good localization in both models and was excreted mainly via liver and to some extent via kidney. Imaging can be performed at 1-2 h post-injection; at that time, the background activity has cleared, and the activity is concentrated in the target site. All the gathered biological data supported the usefulness of 99mTc-olsalazine as a potential imaging agent for ulcerative colitis. [ABSTRACT FROM AUTHOR]

• A rapid and sensitive HILIC-MS/MS method was developed for determining Olsalazine, 5-ASA, and N-Ac-5-ASA. • The effect of L. acidophilus on the metabolism of Olsalazine was evaluated using pharmacokinetic and gut microbiota analyses. • L. acidophilus did not raise the colonic exposure of 5-ASA to achieve a better therapeutic efficacy of combination therapy. • There was no potential medication risk of combination therapy of Olsalazine and L. acidophilus. • L. acidophilus played its role in the treatment of UC by regulating gut microbiota composition and amino acid, phenolic acid, oligosaccharide, and peptidoglycan metabolic pathways. Olsalazine is a typical 5-aminosalicylic acid (5-ASA) drug that depends on gut microbiota to liberate its anti-inflammatory moiety 5-ASA in the treatment of ulcerative colitis (UC). In recent decades, 5-ASA drugs combined with probiotics have achieved a better effective treatment for UC. Mechanisms of combination therapy have been widely discussed from a pharmacodynamic perspective. However, it is still unclear whether the better therapeutic efficacy of combination therapy was made by changing the metabolism of 5-ASA drugs in the colon under the regulation of probiotics. In the present study, combined with pharmacokinetic and gut microbiota analyses, we systematically evaluated the potential effect of Lactobacillus acidophilus (L. acidophilus) on the metabolism of Olsalazine at three levels (pharmacokinetic characteristics, metabolic microbiota, and metabolic enzymes) to offer some insights into this issue. As pharmacokinetic results showed, L. acidophilus barely had an influence on the pharmacokinetic parameters of Olsalazine, 5-ASA, and N-Ac-5-ASA. Notably, the colonic exposure of 5-ASA was not affected by L. acidophilus. Gut microbiota results also illustrated that L. acidophilus did not change the total abundance of azoreductase (azoR) and N-acetyltransferase (NAT) associated gut microbiota and enzymes, which are involved in the metabolism of Olsalazine. Both pharmacokinetic and gut microbiota results revealed that L. acidophilus did not increase the colonic exposure of 5-ASA to improve the efficacy of combination therapy. L. acidophilus played its role in UC treatment by regulating gut microbiota composition and amino acid, phenolic acid, oligosaccharide, and peptidoglycan metabolic pathways. There was no potential medication risk of combination therapy of Olsalazine and L. acidophilus. In summary, this research provided strong evidence of medication safety and a comprehensive understanding of therapeutic advantages for combination therapy of probiotics and 5-ASA drugs from the pharmacokinetic and gut microbiota perspectives. [Display omitted] Pharmacokinetic and gut microbiota analyses revealed the effect of L. acidophilus on the metabolism of Olsalazine in UC rats. [ABSTRACT FROM AUTHOR]

Azo-bonded prodrugs of 5-aminosalicylic acid (mesalazine)-sulfasalazine, balsalazide, and olsalazine, which are used in the treatment of ulcerative colitis, rely on colonic bacteria to cleave the azo bond and liberate the active drug in the large intestine. The aim of this study was to use an in vitro colonic simulator to determine the rates of metabolism of these three prodrugs in the presence of colonic bacteria, and to link the data to results obtained previously in humans. In individual fecal slurries prepared from five different donors, sulfasalazine degradation was rapid and virtually complete within 4 h, confirming the ubiquitous nature of azo-reduction between individuals. In pooled fecal slurry, the rate of degradation of sulfasalazine was faster ( t1/2, 32.8 min) than balsalazide ( t1/2, 80.9 min) and olsalazine ( t1/2, 145.1 min). These results are in agreement with data in humans, where it was found that sulfasalazine was more extensively metabolized on passage through the human colon than the other two drugs. These findings indicate that other than the azo bond itself, the broader chemical structure of the molecules play a role in the degradation of this class of compound, and highlight the utility of this in vitro model to evaluate the metabolism of drugs in the presence of colonic microbiota. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3171-3175, 2014 [ABSTRACT FROM AUTHOR]

Objective. Most previous studies have failed to demonstrate any effect of maternal use of 5-aminosalicylates (5-ASA) on malformation risk, but the number of infants studied have, in most cases, been low. The objective of the study was to get data from a large study with prospectively ascertained exposure information. Material and methods. The study was based on data in the Swedish Medical Birth Register (1996-2011) where identification of maternal drug use is made from midwife interviews in early pregnancy. The presence of congenital malformations was ascertained from three national registers. Adjusted odds ratios were calculated by the Mantel-Haenszel methodology. Results. Among 1,552,109 women, 3651 with 3721 infants had reported the use of 5-ASAs in early pregnancy. The risk of a major malformation was increased (1.37, 95% confidence interval = 1.17-1.62) and still more for a cardiovascular defect (1.74, 1.37-2.22). This effect seemed to be influenced by concomitant use of systemic glucocorticosteroids or immunosuppressants but some confounding by indication may also exist. There was no marked difference between the four 5-ASA drugs studied. Conclusions. Infants born of women who use 5-ASA drugs in early pregnancy have an increased risk of a congenital malformation, notably a cardiovascular defect. This could be a drug effect or an effect of an active inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Abstract: The first two three-dimensional (3D) pillared metal–olsalazine complexes, namely [Co(osa)0.5(bim)0.5(H2O)] (1) and [Cd(osa)0.5(bim)0.5(H2O)] (2) (H4osa=3,3-azo-bis(6-hydroxybenzoic acid), bim=1,4-bis(imidazol-1-yl)butane) have been hydrothermally synthesized and further characterized by single-crystal X-ray diffraction, powder X-ray diffraction, elemental analysis, IR spectra and TG analyses. Compounds 1 and 2 are isostructural, and their frameworks are composed of infinite rod-shaped secondary building units (SBUs) that are bridged by osa ligands to form 2D layers, which are further pillared by bim ligands in the third dimension. To the best of our knowledge, it is the first time that 3D pillared-layer frameworks involving infinite rod-shaped SBUs have been obtained in the realm of metal–olsalazine complexes. The magnetic property of 1 and photoluminescence of 2 have also been investigated. [Copyright &y& Elsevier]

Abstract: Purpose: To compare the degradation kinetics of metronidazole and olsalazine by the bacteria of ascending colon and the bacteria of feces of healthy adults. Methods: Contents of the ascending colon of seven healthy adults were collected under conditions simulating the bioavailability/bioequivalence studies in the fasted and in the fed states on a crossover basis. Material from the contents of the ascending colon was prepared by ultracentrifuging and diluting the precipitate with a volume of normal saline equivalent to that of the supernatant. Fecal material was prepared from feces of three healthy adults collected at two occasions that were separated by at least 6 months. Ex vivo drug degradation kinetics were evaluated under anaerobic conditions. Results: Mean half-lives of metronidazole degradation in material from the contents of the ascending colon collected in the fasted state and in fecal material were 16.1 and 2.4min, respectively (p <0.001). The corresponding numbers for olsalazine were 57.8 and 9.2min, respectively (p <0.001). Both compounds were stable in material from the contents of ascending colon collected in the fed state. Conclusions: Compared with data in fecal material, degradation of metronidazole and olsalazine in material from the contents of the ascending colon is significantly slower and it becomes non-significant during the arrival of fresh food remnants in the region. [Copyright &y& Elsevier]

Abstract: A bismuth film electrode (BiFE) prepared ex-situ on a supporting glassy carbon electrode exhibited convenient electroanalytical performance for voltammetric measurement of selected aminosalycilate drugs. The reduction behaviour of aminosalycilate drugs was studied in aqueous solutions within the pH range of 4–6. The voltammetric responses were compared with those obtained at the bare glassy carbon electrode under identical conditions. In the square-wave voltammetric operation mode the BiFE showed a linear response in the concentration range of 5×10−6 to 3.5×10−4 and 1×10−6 to 5×10−4 M for sulfasalazine and olsalazine, respectively. Its electrode surface revealed auspiciously high stability and remarkable reproducibility in the rapid analysis of aminosalycilate drugs. Finally, the BiFE was satisfactorily applied for direct quantitation of azo prodrugs in real pharmaceutical samples. [Copyright &y& Elsevier]

Two 1-D linear coordination polymers, {[Gd2(L)2 · (Phen)2 · 2(H2O) · 2(NO3)] · 2(EtOH)}n (1) (H2L = olsalazine) and {[Eu2(L)2·(Phen)2 · 2(H2O) · 2(NO3)] · EtOH}n (2), were obtained from self-assembly of Gd(NO3)3 · 8H2O or Eu(NO3)3 · 8H2O with olsalazine. Both complexes are 1-D polymers, for 1 with crystal data: P 1, a = 11.651(4), b = 11.865(4), and c = 12.296(4) Å, α = 77.984(4)°, β = 65.559(4)°, and γ = 74.558(5)°, V = 1482.1(8) Å3, Z = 1, R1 = 0.0389, wR2 = 0.0793, and 2 with crystal data: P 1, a = 11.626(3), b = 11.834(3), c = 12.287(4) Å, α = 77.743(3), β = 65.576(3), γ = 74.371(3)°, V = 1472.5(5) Å3, Z = 1, R1 = 0.0609, wR2 = 0.1185. Central atoms (Gd or Eu) in both complexes adopt nine-coordinate tricapped trigonal prism geometry. CCDC No.: 694918 (1), 694919 (2). [ABSTRACT FROM AUTHOR]