Prevention of colitis by controlled oral drug delivery of carbon monoxide

Steiger, Christoph; Uchiyama, Kazuhiko; Takagi, Tomohisa; Mizushima, Katsura; Higashimura, Yasuki; Gutmann, Marcus; Hermann, Cornelius; Botov, Svetlana; Schmalz, Hans‐Günther; Naito, Yuji; Meinel, Lorenz

doi:10.1016/j.jconrel.2016.08.030

Cited by 48 publications

(41 citation statements)

References 55 publications

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“…The tablets showed protection from colitis by a reduced colon damage score and a maximal CO-Hb limit of 1.4% (safety threshold: 5-10% CO-Hb). 8,63 MnCORM@Al-MCM-41 nanoparticles…”

Section: Encapsulated Cormsmentioning

confidence: 99%

“…Indeed these in vitro data of the CO release are only available for some conjugates and these results could differ from the in vivo profiles. For application of the conjugates, additional in vivo data should be analyzed and compared to the in vitro results as has appeared to have been done for the first time by the group of Meinel et al 63 The same as CORMs in solution, these conjugates play a key role in the pharmacokinetic parameters. They are prodrugs and their action is completely dependent on the in vivo constraints.…”

Section: Conclusion/personal Viewmentioning

confidence: 99%

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CO-releasing molecule (CORM) conjugate systems

2016

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The development of CORMs (CO-releasing molecules) as a prodrug for CO administration in living organisms has attracted significant attention. CORMs offer the promising possibility of a safe and controllable release of CO in low amounts triggered by light, ligands, enzymes, etc. For the targeting of specific tissues or diseases and to prevent possible side effects from metals and other residues after CO release, these CORMs are attached to biocompatible systems, like peptides, polymers, nanoparticles, dendrimers, protein cages, non-wovens, tablets, and metal-organic frameworks. We discuss in this review the known CORM carrier conjugates, in short CORM conjugates, with covalently-bound or incorporated CORMs for medicinal and therapeutic applications. Most conjugates are nontoxic, show increasing half-lives of CO release, and make use of the EPR-effect, but still show problems because of a continuous background of CO release and the absence of an on/off-switch for the CO release.

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“…The tablets showed protection from colitis by a reduced colon damage score and a maximal CO-Hb limit of 1.4% (safety threshold: 5-10% CO-Hb). 8,63 MnCORM@Al-MCM-41 nanoparticles…”

Section: Encapsulated Cormsmentioning

confidence: 99%

Section: Conclusion/personal Viewmentioning

confidence: 99%

CO-releasing molecule (CORM) conjugate systems

2016

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“…The CO release profiles were recorded in a custom‐made measurement cell consisting of two DN25 flanges (bottom closed, Rettberg, Göttingen, Germany) equipped with a XXS CO probe from Dräger (Lübeck, Germany) , . The probe was connected to an X‐am 5000 gas sensor (Dräger).…”

Section: Methodsmentioning

confidence: 99%

Wavelength‐Dependent Control of the CO Release Kinetics of Manganese(I) Tricarbonyl PhotoCORMs with Benzimidazole Coligands

et al. 2019

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A series of photoactivatable CO‐releasing molecules (PhotoCORMs) was prepared from manganese pentacarbonyl bromide and 1H‐benzimidazol‐2‐ylmethyl‐(N‐phenyl)amine ligands (L) bearing different electron‐donating and electron‐withdrawing groups R = H, 4‐CH3, 4‐OCH3, 4‐Cl, 4‐NO2, 2‐, 3‐, and 4‐COOCH3 on the phenyl substituent to give octahedral manganese(I) complexes of the general formula [MnBr(CO)3(L)]. Aerated DMSO solutions of the compounds are stable in the dark for 16 h with no CO release. However, the compounds rapidly release CO upon illumination at 412–525 nm, depending on the substitution pattern. Its influence on the photophysical and photochemical properties was systematically explored using UV/Vis spectroscopy and CO release measurements with a commercial gas sensor system. In the nitro‐substituted compound, the electronically excited state switched from benzimidazole‐ to phenyl‐centered, leading to a markedly different photochemical behavior of this visible‐light activated PhotoCORM.

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“…Orally administering a tablet of approximately 1 mm in size significantly inhibited trinitrobenzenesulfonic acid-induced colitis in mice. ( 22 ) Recently, we explored the efficacy and mechanisms of action of CORMs in a T-cell transfer-induced colitis model in mice. The results showed that CORMs conferred protection against the development of intestinal inflammation and attenuated Th17 cell differentiation.…”

Section: Co As An Anti-inflammatory Mediatormentioning

confidence: 99%

Redox-related gaseous mediators in the gastrointestinal tract

Naito

Uchiyama

Takagi

2018

J. Clin. Biochem. Nutr.

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Redox-related gaseous molecular species in the gastrointestinal tract are derived from the chemical oxidation-reduction reactions, enzymatic reactions, swallowing, and bacterial production. Recent studies have demonstrated the crucial roles of the microbiota and gaseous molecules in the pathogenesis of gastrointestinal inflammatory and functional diseases. Especially in the hypoxic condition of the large intestine, various bacteria produce acetic acid, methane, and hydrogen sulfide using hydrogen molecules generated by the fermentation reaction as an energy source. In this review, we summarized the recent advances in the biology of redox-related gaseous molecules in the gastrointestinal tract.

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Prevention of colitis by controlled oral drug delivery of carbon monoxide

Cited by 48 publications

References 55 publications

CO-releasing molecule (CORM) conjugate systems

CO-releasing molecule (CORM) conjugate systems

Wavelength‐Dependent Control of the CO Release Kinetics of Manganese(I) Tricarbonyl PhotoCORMs with Benzimidazole Coligands

Redox-related gaseous mediators in the gastrointestinal tract

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