Discovery and preclinical development of a novel prodrug conjugate of mesalamine with eicosapentaenoic acid and caprylic acid for the treatment of inflammatory bowel diseases

Kandula, Mahesh; Kumar, KB Sunil; Palanichamy, Sivanesan; Rampal, Ashok

doi:10.1016/j.intimp.2016.09.013

Cited by 17 publications

(8 citation statements)

References 23 publications

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“…Systemic exposure of the prodrug and 5‐ASA was low, indicating a better safety profile. Pharmacologically, disease activity index (DAI) was improved, myeloperoxidase activity reduced, and colonic histological scores were comparable to that achieved by sulfasalazine . Overall, this FA‐based prodrug showed significant potential for improved IBD drug therapy.…”

Section: Lipidic Prodrugs As a Mean For Enhancing Oral Drug Delivery:mentioning

confidence: 81%

“…Some lipids exhibit the pharmacological activity of their own, and matching such lipidic carriers with complementary drug moiety can provide a significant benefit: after activation, each prodrug molecule will produce two active moieties, the drug and the pharmacologically active lipid, and the overall therapeutic effect may be improved . Lipidic prodrugs can also aid in overcoming the metabolic/chemical instability of the free drug …”

Section: Discussionmentioning

confidence: 99%

“…A double FA prodrug of 5‐ASA, conjugated with eicosapentaenoic acid and caprylic acid (CLX‐103; Table ), was developed aiming to release the free drug at the target sites, the ileum, and the colon. The two ester bonds were expected to provide controlled release of 5‐ASA to the target sites, while minimizing systemic absorption . CLX‐103 was shown to be stable in the gastric environment, but was hydrolyzed after passing into the small intestine, releasing 5‐ASA.…”

Section: Lipidic Prodrugs As a Mean For Enhancing Oral Drug Delivery:mentioning

confidence: 99%

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Lipidic prodrug approach for improved oral drug delivery and therapy

Marković

Ben‐Shabat

Keinan

et al. 2018

Medicinal Research Reviews

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In the past, a prodrug design was used as a last option to improve bioavailability through controlling transport, distribution, metabolism, or other mechanisms. Prodrugs are currently used even in early stages of drug development, and a significant percentage of all drugs in the market are prodrugs. The focus of this article is lipidic prodrugs, a strategy whereby a lipid carrier is covalently bound to the drug moiety. The increased lipophilicity of the lipid-drug conjugate can improve the pharmacokinetic profile and provide meaningful advantages: increased absorption across biological barriers, prolonged circulation half-life, selective distribution profile (eg brain penetration), reduced hepatic first-pass metabolism, and overall enhanced bioavailability of the parent drug. Moreover, lipidic prodrugs may join the endogenous lipid trafficking pathways, thereby facilitate drug targeting, either by selective absorption pathway (eg lymphatic transport) or drug release at specific target site(s).The different lipid-drug conjugates (triglyceride-, fatty acids, phospholipid-, and steroid-based prodrugs), the physiological barriers that challenge the absorption of these conjugates, followed by their current utilization and potential clinical benefits are described and analyzed, and future opportunities this approach could provide are discussed.Altogether, lipidic prodrugs represent an exciting approach for improving different aspects of oral drug delivery/therapy and may provide solutions for various unmet needs; the use of this strategy is expected to grow.

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Section: Lipidic Prodrugs As a Mean For Enhancing Oral Drug Delivery:mentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Lipidic Prodrugs As a Mean For Enhancing Oral Drug Delivery:mentioning

confidence: 99%

See 1 more Smart Citation

Lipidic prodrug approach for improved oral drug delivery and therapy

Marković

Ben‐Shabat

Keinan

et al. 2018

Medicinal Research Reviews

View full text Add to dashboard Cite

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“…The experimental studies showed that the maximum therapeutic efficacy was attained with the co-administration of the two prepared minitablets and probiotics compared to that with the single administration of mesalamine minitablets, modified apple polysaccharide minitablets or probiotics alone. Kandula et al [38] synthesized CLX-103 as a novel prodrug conjugate of mesalamine, eicosapentaenoic acid and caprylic acid, to achieve a colon targeted mesalamine delivery with enhanced safety and therapeutic efficacy. In vitro and In vivo studies showed that CLX-103 was biochemically stable in simulated gastric fluid and underwent enzymatic hydrolysis in the intestinal environment to releases mesalamine, which stayed a longer period of time in the large intestine compared to sulfasalazine.…”

Section: Microbial/enzyme Sensitive Approachmentioning

confidence: 99%

Recent advances in mesalamine colonic delivery systems

Bayan

2020

Futur J Pharm Sci

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Background: Increased attention has been focused on the continuous development and improvement of mesalamine colonic specific delivery systems, for the effective treatment of inflammatory bowel diseases; thus enhancing therapeutic efficacy and reducing potential side effects. Mesalamine is a class IV drug, according to the Biopharmaceutics Classification System, used usually to treat inflammation associated with colon related diseases such as Crohn's disease and ulcerative colitis. Main text An ideal colon targeting system aims to deliver a therapeutic agent, selectively and effectively, to the colon. This system should ideally retain the drug release in the upper GI tract (stomach and small intestine); while trigger the drug release in the colon. Several approaches have been used to fabricate formulations to achieve a colon specific delivery of mesalamine such as; time dependent, pH responsive, enzymatic/microbial responsive and ultrasound mediated approaches. This overview outlines the recent advances in mesalamine-colon delivery approaches for the potential treatment of ulcerative colitis and Crohn' disease. Conclusion: A combined pH-time dependent delivery system can improve mesalamine colonic drug delivery via employing carriers capable of retarding mesalamine release in the stomach and delivering it at predetermined time points after entering the intestine. The existence of specific enzymes, produced by various anaerobic bacteria present in the colon advocates the advantage of designing enzyme sensitive systems and combining it with pHtime dependent system to improve mesalamine colonic delivery. The use of ultrasound has shown promises to effectively treat inflammatory bowel diseases.

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“…In order to circumvent the effects of RA, sulfasalazine (SSZ) is considered as a first line treatment which is on the World Health Organization's list of necessary medicines [3,4] . SSZ which is an anti‐inflammatory drug belongs to the aminosalicylate category and is widely prescribed for the cure of bowel disease [5,6] . It is also effective in the treatment of ulcerative colitis and Crohn's disease [7–9] .…”

Section: Introductionmentioning

confidence: 99%

Trace Level Recognition of Sulfasalazine Electrooxidation Exploiting the Synergism of Carbon Nanotubes and Iron Oxide Nanoparticles

Mane

Chatterjee

2021

ChemistrySelect

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The significance of sulfasalazine (SSZ) as a therapeutic agent has garnered paramount research interest in the design and fabrication of a viable sensor for the detection of SSZ. Herein, we demonstrate a new strategy for the sensitive determination of SSZ employing single walled carbon nanotubes decorated with Fe3O4 nanoparticles sensing platform for the first time. The synthesized Fe3O4 nanoparticles and the surface morphology of the developed sensor were investigated by exerting various analytical techniques. The optimization of operational parameters was effectuated. The developed sensor exhibited pronounced electrocatalytic activity for the electro oxidation of SSZ in the dynamic detection range of 25 nM–1.5 μM manifesting noteworthy high sensitivity and phenomenal low detection limit of 18.6 μA μM−1 and 1.6 nM respectively. Apparent specificity in the presence of interferents along with remarkable stability and reproducibility were attained by the sensor. The prominence of the developed methodology was emphasized by the determination of SSZ in pharmaceutical formulations. Furthermore, the applicability of the developed electrode was established by utilizing it effectually for the first time to quantify SSZ in serum sample of patients undergoing pharmacological treatment for rheumatoid arthritis.

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Discovery and preclinical development of a novel prodrug conjugate of mesalamine with eicosapentaenoic acid and caprylic acid for the treatment of inflammatory bowel diseases

Cited by 17 publications

References 23 publications

Lipidic prodrug approach for improved oral drug delivery and therapy

Lipidic prodrug approach for improved oral drug delivery and therapy

Recent advances in mesalamine colonic delivery systems

Trace Level Recognition of Sulfasalazine Electrooxidation Exploiting the Synergism of Carbon Nanotubes and Iron Oxide Nanoparticles

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