Reposition of the anti-inflammatory drug diacerein in an in-vivo colorectal cancer model

Background: Colorectal cancer (CRC) is the third most common cancer in the world. 5-Fluorouracil (5-FU) is a conventional and most effective drug used in the clinic for the treatment of CRC. However, the clinical use of 5-FU is limited due to the acquired resistance and systemic toxicity, such as hepatotoxicity and gastrointesti-nal toxicity. Objective: Recent advances in nanomedicine are being exploited to develop nanoparticle platforms to overcome resistance and therapeutic delivery of active molecules. Here, we develop 5-FU loaded sulfadiazine-poly(lactide-co-glycolide) nanoparticles (SUL-PLGA NPs) to be applied in the colorectal cancer model. Methods: We assessed the in vivo efficacy of the SUL-PLGA NPs to enhance the antitumor effect of 5-FU. Results: In vivo treatment with 5-FU-SUL-PLGA NPs significantly reduced tumor growth in a colon cancer xen-ograft model compared to free 5-FU and 5-FU loaded non-targeted NPs. Treatment with 5-FU-SUL-PLGA NPs also increased blood vessel diameters within tumors, which could act in conjunction to enhance antitumor effi-cacy. In addition, 5-FU-SUL-PLGA NPs significantly reduced liver mass and lung mass, which are the most common metastasis sites of CRC, and decreased liver hepatotoxicity compared to free 5-FU drug and 5-FU loaded non-targeted NPs. Conclusion: Our findings suggest that the use of 5-FU-SUL-PLGA NPs is a promising strategy to enhance 5-FU efficacy against CRC.

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546 Genome-Wide Gene-Environment Interaction Analysis of Aspirin and Non-Steroidal Anti-Inflammatory Drug Use and Colorectal Cancer Identifies Loci At Chromosomes 12p12.3 and 15q25.2

Gastroenterology ◽

10.1016/s0016-5085(14)60354-1 ◽

2014 ◽

Vol 146 (5) ◽

pp. S-97

Author(s):

Hongmei Nan ◽

Carolyn Hutter ◽

Yi Lin ◽

Cornelia M Ulrich ◽

Emily White ◽

...

Keyword(s):

Colorectal Cancer ◽

Drug Use ◽

Interaction Analysis ◽

Environment Interaction ◽

Inflammatory Drug ◽

Gene Environment Interaction ◽

Gene Environment ◽

Genome Wide ◽

Anti Inflammatory

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Reversion of antibiotic resistance in drug-resistant bacteria using non-steroidal anti-inflammatory drug benzydamine

10.1101/2021.05.07.443075 ◽

2021 ◽

Author(s):

Yuan Liu ◽

Ziwen Tong ◽

Jingru Shi ◽

Tian Deng ◽

Ruichao Li ◽

...

Keyword(s):

Cost Effective ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Inflammatory Drug ◽

Development Of Resistance ◽

Drug Resistant Bacteria ◽

Metabolic States ◽

Anti Inflammatory ◽

Approved Drugs

Antimicrobial resistance has been a growing concern that gradually undermines our tradition treatment regimen. The fact that few antibacterial drugs with new scaffolds or targets have been approved in the past two decades aggravates this crisis. Repurposing previously approved drugs as potent antibiotic adjuvants offers a cost effective strategy to mitigate the development of resistance and tackle the increasing infections by multidrug resistant (MDR) bacteria. Herein, we found that benzydamine, a widely used non-steroidal anti-inflammatory drug in clinic, remarkably potentiated broad spectrum antibiotic tetracyclines activity against a panel of clinical important resistant pathogens, including MRSA, VRE, MCRPEC and tet (X)-positive Gram negative bacteria. Further mechanistically experiments showed that benzydamine dissipated membrane potential (ΔΨ) in both Gram positive and negative bacteria, which in turn upregulated the transmembrane proton gradient (ΔpH) and promoted the uptake of tetracyclines. Additionally, benzydamine exacerbated the oxidative stress by triggering the production of ROS and suppressing GAD system mediated oxidative defensive. This mode of action explains the great bactericidal activity of the doxycycline benzydamine combination against different metabolic states of bacteria including persister cells. As a proof of concept, the in vivo efficacy of this combination therapy was evidenced in multiple animal infection models. These findings revealed that benzydamine is a promising tetracycline antibiotics adjuvant and has the potential to address life threatening infections by MDR bacteria.

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A novel dual-prodrug carried by cyclodextrin inclusion complex for the targeting treatment of colon cancer

Journal of Nanobiotechnology ◽

10.1186/s12951-021-01064-3 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Lin Chen ◽

Yan Lin ◽

Zijun Zhang ◽

Ruisheng Yang ◽

Xiaosheng Bai ◽

...

Keyword(s):

Colorectal Cancer ◽

Ulcerative Colitis ◽

Colon Cancer ◽

Inclusion Complex ◽

Tumor Suppression ◽

Folate Receptor ◽

Significant Inhibition ◽

Aminosalicylic Acid ◽

Anti Inflammatory

Abstract Background There is an obvious correlation between ulcerative colitis and colorectal cancer, and the risk of colorectal cancer in patients with ulcerative colitis is increasing. Therefore, the combination therapy of anti-inflammatory and anti-tumor drugs may show promising to inhibit colon cancer. 5-aminosalicylic acid (5-ASA) with anti-inflammatory function is effective for maintaining remission in patients with ulcerative colitis and may also reduce colorectal cancer risk. Histone deacetylase (HDAC) plays an essential role in the progression of colon cancer. Butyric acid (BA) is a kind of HDAC inhibitor and thus shows tumor suppression to colon cancer. However, the volatile and corrosive nature of BA presents challenges in practical application. In addition, its clinical application is limited due to its non-targeting ability and low bioavailability. We aimed to synthesize a novel dual-prodrug of 5-ASA and BA, referred as BBA, to synergistically inhibit colon cancer. Further, based on the fact that folate receptor (FR) is over-expressed in most solid tumors and it has been identified to be a cancer stem cell surface marker in colon cancer, we took folate as the targeting ligand and used carboxymethyl-β-cyclodextrin (CM-β-CD) to carry BBA and thus prepared a novel inclusion complex of BBA/FA-PEG-CM-β-CD. Results It was found that BBA/FA-PEG-CM-β-CD showed significant inhibition in cell proliferation against colon cancer cells SW620. It showed a pro-longed in vivo circulation and mainly accumulated in tumor tissue. More importantly, BBA/FA-PEG-CM-β-CD gave great tumor suppression effect against nude mice bearing SW620 xenografts. Conclusions Therefore, BBA/FA-PEG-CM-β-CD may have clinical potential in colon cancer therapy. Graphical Abstract

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Development, in-vitro and in-vivo characterization of gelatin nanoparticles for delivery of an anti-inflammatory drug

Journal of Drug Delivery Science and Technology ◽

10.1016/j.jddst.2016.09.007 ◽

2016 ◽

Vol 36 ◽

pp. 55-61 ◽

Cited By ~ 10

Author(s):

Alok Mahor ◽

Sunil Kumar Prajapati ◽

Amita Verma ◽

Rishikesh Gupta ◽

Thakur Raghu Raj Singh ◽

...

Keyword(s):

Gelatin Nanoparticles ◽

Inflammatory Drug ◽

Anti Inflammatory ◽

Development In Vitro ◽

In Vivo Characterization

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Inhibitory Effect of Herbal Remedy PERVIVO and Anti-Inflammatory Drug Sulindac on L-1 Sarcoma Tumor Growth and Tumor Angiogenesis in Balb/c Mice

Mediators of Inflammation ◽

10.1155/2013/289789 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

P. Skopiński ◽

B. J. Bałan ◽

J. Kocik ◽

R. Zdanowski ◽

S. Lewicki ◽

...

Keyword(s):

Tumor Growth ◽

Tumor Angiogenesis ◽

Herbal Remedy ◽

Inhibitory Effect ◽

Inflammatory Drug ◽

Anticancer Effects ◽

Biologic Response ◽

Inflammatory Drugs ◽

Anti Inflammatory

Anticancer activity of many herbs was observed for hundreds of years. They act as modifiers of biologic response, and their effectiveness may be increased by combining multiple herbal extracts . PERVIVO, traditional digestive herbal remedy, contains some of them, and we previously described its antiangiogenic activity. Numerous studies documented anticancer effects of nonsteroidal anti-inflammatory drugs. We were the first to show that sulindac and its metabolites inhibit angiogenesis. In the present paper the combinedin vivoeffect of multicomponent herbal remedy PERVIVO and nonsteroidal anti-inflammatory drug sulindac on tumor growth, tumor angiogenesis, and tumor volume in Balb/c mice was studied. These effects were checked after grafting cells collected from syngeneic sarcoma L-1 tumors into mice skin. The strongest inhibitory effect was observed in experimental groups treated with PERVIVO and sulindac together. The results of our investigation showed that combined effect of examined drugs may be the best way to get the strongest antiangiogenic and antitumor effect.

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