Colonic delivery of metronidazole-loaded capsules for local treatment of bacterial infections: A clinical pharmacoscintigraphy study

Preisig, Daniel; Varum, Felipe; Bravo, Roberto; Hartig, C.; Spleiss, Johannes; Abbes, Sonia; Caobelli, Federico; Wild, Damian; Puchkov, Maxim; Haschke, Manuel

doi:10.1016/j.ejpb.2021.05.002

Cited by 13 publications

(9 citation statements)

References 52 publications

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“…Moreover, one can use imaging methods, such as gamma-scintigraphy, magnetic marker monitoring and magnetic resonance imaging [19,79,153], as well as data on fecal concentrations as in vivo markers. However, many of these investigations are costly and time intense and, in the case of imaging technologies, do not provide information on the active moiety release but on the labelled moiety (but does provide information on the site of disintegration, however).…”

Section: Considerations For In Vivo Methodsmentioning

confidence: 99%

“…The recently launched OPTICORE™ technology was developed in order to overcome the inherent variability in transit time and accelerate drug release once a pH or enzymatic trigger is initiated. It comprises a combination of enteric polymer and polysaccharide as an outer layer (Phloral™) and an inner alkaline layer that promotes faster coating dissolution [63,79,80]. This technology was a key enabler for the successful phase 3 study of a 1600 mg mesalazine product in mild-to-moderate ulcerative colitis patients, which led to the launch of Asacol ® 1600 mg (also marketed as Asacolon ® 1600 mg and Yaldigo ® 1600 mg), now marketed in multiple countries.…”

Section: Enzymatic Triggered Release Systemsmentioning

confidence: 99%

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In Vitro Methodologies for Evaluating Colon-Targeted Pharmaceutical Products and Industry Perspectives for Their Applications

et al. 2022

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Several locally acting colon-targeted products to treat colonic diseases have been recently developed and marketed, taking advantage of gastrointestinal physiology to target delivery. Main mechanisms involve pH-dependent, time-controlled and/or enzymatic-triggered release. With site of action located before systemic circulation and troublesome colonic sampling, there is room for the introduction of meaningful in vitro methods for development, quality control (QC) and regulatory applications of these formulations. A one-size-fits-all method seems unrealistic, as the selection of experimental conditions should resemble the physiological features exploited to trigger the release. This article reviews the state of the art for bio-predictive dissolution testing of colon-targeted products. Compendial methods overlook physiological aspects, such as buffer molarity and fluid composition. These are critical for pH-dependent products and time-controlled systems containing ionizable drugs. Moreover, meaningful methods for enzymatic-triggered products including either bacteria or enzymes are completely ignored by pharmacopeias. Bio-predictive testing may accelerate the development of successful products, although this may require complex methodologies. However, for high-throughput routine testing (e.g., QC), simplified methods can be used where balance is struck between simplicity, robustness and transferability on one side and bio-predictivity on the other. Ultimately, bio-predictive methods can occupy a special niche in terms of supplementing plasma concentration data for regulatory approval.

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Section: Considerations For In Vivo Methodsmentioning

confidence: 99%

Section: Enzymatic Triggered Release Systemsmentioning

confidence: 99%

In Vitro Methodologies for Evaluating Colon-Targeted Pharmaceutical Products and Industry Perspectives for Their Applications

et al. 2022

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“…Colitis lesions are mainly limited to the mucosa, submucosa of the colon, and can diffuse to the entire colon [ 33 ]. After orally administration, drug ingredients are usually absorbed by intestinal villi and across the mucosa to the blood by passive diffusion, which then distribute to colonic tissues [ 34 , 35 ]. Besides, drug ingredients that are not absorbed by intestinal villi can be absorbed by colonic epithelial mucosa, which may exert influence on colitis directly [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic material basis and underling mechanisms of Shaoyao Decoction-exerted alleviation effects of colitis based on GPX4-regulated ferroptosis in epithelial cells

Tian

et al. 2022

Chin Med

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Background Shaoyao Decoction (SYD) is a canonical herbal medicine prescription formulated by Liu Wan-Su in AD 1186. SYD has been widely used to treat inflammatory bowel disease by clearing heat and damp, removing stasis toxin in the intestine; however, the precise mechanisms and therapeutic material basis remain largely unclear. In the present study, we measured the effects of SYD on colitis symptom, epithelial barrier function, epithelial ferroptosis, colonic protein and mRNA expression of glutathione peroxidase 4 (GPX4) in colitis model, and determined whether SYD restored barrier loss in colitis by modulation of GPX4-regulated ferroptosis pathway. Methods Colitis was established by infusion with 1 mL 2,4,6-trinitrobenzene sulfonic acid (TNBS) dissolved in ethanol (40% v/v) in rats at a 125 mg/kg dose. Ferroptosis in epithelial cells was determined by flow cytometer. GPX4 promoter-firefly luciferase fusion construct was transfected to Caco-2 cell to determine GPX4 transcription. MS analysis was used to identified ingredients in SYD. Results Different doses of SYD significantly alleviated colitis, decreased ferroptosis in epithelial cells, knockout of GPX4 significantly reversed SYD-induced alleviation effects on colitis, restoration of epithelial barrier function, and epithelial ferroptosis. Wogonoside, wogonin, palmatine, paeoniflorin and liquiritin were identified as active ingredients of SYD-exerted alleviation effects of colitis based on GPX4 agonistic transcription. Conclusion SYD alleviated chemically induced colitis by activation of GPX4, inhibition of ferroptosis in epithelial cells and further restoration of barrier function. Wogonoside, wogonin, palmatine, paeoniflorin and liquiritin were identified as the key therapeutic material basis of SYD-exerted anti-colitis effects. The findings provide a scientific basis for the therapeutic effect of SYD on colitis.

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“…A recent phase I clinical trial used the OPTICORE TM technology for the targeted delivery of metronidazole benzoate to treat localised colonic Clostridioides (formerly Clostridium) difficile (C. diff) infections. Accurate ileo-colonic targeting was achieved with reduced systemic concentrations, compared to immediate-release findings [259]. Additionally, Asacol™ 1600 mg, a 5-ASA product based on the OPTICORE™ technology, has successfully passed Phase III clinical trials and been marketed in Europe [260].…”

Section: Opticore™mentioning

confidence: 99%

Clinical translation of advanced colonic drug delivery technologies

Awad

Madla

McCoubrey

et al. 2022

Advanced Drug Delivery Reviews

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Colonic delivery of metronidazole-loaded capsules for local treatment of bacterial infections: A clinical pharmacoscintigraphy study

Cited by 13 publications

References 52 publications

In Vitro Methodologies for Evaluating Colon-Targeted Pharmaceutical Products and Industry Perspectives for Their Applications

In Vitro Methodologies for Evaluating Colon-Targeted Pharmaceutical Products and Industry Perspectives for Their Applications

Therapeutic material basis and underling mechanisms of Shaoyao Decoction-exerted alleviation effects of colitis based on GPX4-regulated ferroptosis in epithelial cells

Clinical translation of advanced colonic drug delivery technologies

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