Clinical translation of advanced colonic drug delivery technologies

Awad, Atheer; Madla, Christine M.; McCoubrey, Laura E.; Ferraro, Fabiana; Gavins, Francesca K.H.; Buanz, Asma; Gaisford, Simon; Orlu, Mine; Siepmann, Florence; Siepmann, Juergen; Basit, Abdul W.

doi:10.1016/j.addr.2021.114076

Cited by 72 publications

(51 citation statements)

References 341 publications

(414 reference statements)

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“…Time-controlled systems (B) for which the release can be controlled by employing permeable insoluble polymers (top), such as ethylcellulose, or by an insoluble matrix core, such as hydroxypropyl methyl cellulose (HPMC), carnauba wax (bottom). Enzymatic triggered release systems (C) commonly use pectin, starch, alginate, gums, amylose, chitosan, dextran, chondroitin sulphate, inulin, and galactomannan embedded into a insoluble polymer (i.e., ethylcellulose) or pH-sensitive polymer (methacrylic acid and methyl methacrylate) [66][67][68][69][70].…”

Section: Ph-dependent 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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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: Ph-dependent 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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“…Such formulations aim to reduce absorption from the small intestine to maximize local concentrations at the site of action while limiting systemic exposure and possible adverse effects. For a recent in-depth review of colon-targeted formulations, we refer to Awad et al (2022). For mesalazine, different delivery systems are available to reach the lower segments of the gut, based on prolonged release, pH-or microbiota-triggered release, or combined mechanisms (Lemmens et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

The effect of esomeprazole on the upper GI tract release and systemic absorption of mesalazine from colon targeted formulations

Camp

Vanuytsel

Brouwers

et al. 2022

International Journal of Pharmaceutics

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“…Besides new drugs, advanced colon-targeting delivery systems, which exploit multiple characteristics of the colonic environment and exert their actions in parallel to achieve more robust and reliable site-specific drug delivery, can also be utilized to achieve better therapeutic effects [ 53 ]. This system can be used to realize the targeted delivery of HKL to the colon focal zone for a better therapeutic action of UC in the future.…”

Section: Discussionmentioning

confidence: 99%

Honokiol Ameliorates DSS-Induced Mouse Colitis by Inhibiting Inflammation and Oxidative Stress and Improving the Intestinal Barrier

Wang

2022

Oxidative Medicine and Cellular Longevity

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Ulcerative colitis (UC) is a multifactor intestinal disease with increased morbidity. Recently, pleiotropic drugs with exact biosafety have been urgently needed. Honokiol (HKL) is the major bioactive component of traditional Chinese medicine “Houpu,” with almost no toxic effects and approved anti-inflammation, antioxidant, antispasmodic, etc. effects. This study examined the therapeutic effect of HKL in dextran sulfate sodium- (DSS-) induced experimental colitis. In vivo, C57BL/6 mice received 3% DSS for seven days to generate UC, and HKL was pretreated for five days and given during the whole DSS-induced period. In vitro, RAW264.7 macrophages were stimulated with lipopolysaccharide (LPS) to induce inflammation, and mouse colon epithelial cells (MCEC) were treated with HKL or pretreated with HKL and then stimulated with LPS-induced macrophage supernate to investigate the barrier enhancement roles. HKL significantly ameliorated disease activity index (DAI), colon length, and histopathological scores in DSS-induced colitis. The inflammatory mediators of interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX2) were decreased, and the tight conjunction proteins were increased in the HKL-treated group both in vivo and in vitro. Above all, HKL can relieve experimental UC through anti-inflammation, antioxidant, and epithelial barrier enhancement roles. These effects were associated with peroxisome proliferator-activated receptor γ (PPARγ)/nuclear factor-κB (NF-κB) p65, sirtuin3 (SIRT3)/adenosine 5 ′ -monophosphate- (AMP-) activated protein kinase (AMPK), and nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase 1 (HO1) signaling pathways. In conclusion, after further clinical studies, HKL may be a promising drug for UC.

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Clinical translation of advanced colonic drug delivery technologies

Cited by 72 publications

References 341 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

The effect of esomeprazole on the upper GI tract release and systemic absorption of mesalazine from colon targeted formulations

Honokiol Ameliorates DSS-Induced Mouse Colitis by Inhibiting Inflammation and Oxidative Stress and Improving the Intestinal Barrier

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