Development of novel zero-order release budesonide tablets for the treatment of ileo-colonic inflammatory bowel disease and comparison with formulations currently used in clinical practice

Gareb, Bahez; Dijkstra, Gerard; Kosterink, Jos G. W.; Frijlink, Henderik W.

doi:10.1016/j.ijpharm.2018.11.019

Cited by 25 publications

(8 citation statements)

References 42 publications

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“…Current therapies for IBD, however, are also pursuing intestine-specific delivery of drugs. The ColoPulse technology is such a novel approach which allows controlled release of drugs at the terminal ileum and colon [45]. Systemic and gastrointestinal side effects of pirfenidone may be minimized using such approach, concomitant with a higher drug-efficacy of pirfenidone on intestinal inflammation and fibrosis [46].…”

Section: Discussionmentioning

confidence: 99%

Pirfenidone Inhibits Cell Proliferation and Collagen I Production of Primary Human Intestinal Fibroblasts

Cui

Zhang

Leng

et al. 2020

Cells

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Intestinal fibrosis is a common complication of inflammatory bowel disease. So far, there is no safe and effective drug for intestinal fibrosis. Pirfenidone is an anti-fibrotic compound available for the treatment of idiopathic pulmonary fibrosis. Here, we explored the anti-proliferative and anti-fibrotic properties of pirfenidone on primary human intestinal fibroblasts (p-hIFs). p-hIFs were cultured in the absence and presence of pirfenidone. Cell proliferation was measured by a real-time cell analyzer (xCELLigence) and BrdU incorporation. Cell motility was monitored by live cell imaging. Cytotoxicity and cell viability were analyzed by Sytox green, Caspase-3 and Water Soluble Tetrazolium Salt-1 (WST-1) assays. Gene expression of fibrosis markers was determined by quantitative reverse transcription PCR (RT-qPCR). The mammalian target of rapamycin (mTOR) signaling was analyzed by Western blotting and type I collagen protein expression additionally by immunofluorescence microscopy. Pirfenidone dose-dependently inhibited p-hIF proliferation and motility, without inducing cell death. Pirfenidone suppressed mRNA levels of genes that contribute to extracellular matrix production, as well as basal and TGF-β1-induced collagen I protein production, which was associated with inhibition of the rapamycin-sensitive mTOR/p70S6K pathway in p-hIFs. Thus, pirfenidone inhibits the proliferation of intestinal fibroblasts and suppresses collagen I production through the TGF-β1/mTOR/p70S6K signaling pathway, which might be a novel and safe anti-fibrotic strategy to treat intestinal fibrosis.

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Section: Discussionmentioning

confidence: 99%

Pirfenidone Inhibits Cell Proliferation and Collagen I Production of Primary Human Intestinal Fibroblasts

Cui

Zhang

Leng

et al. 2020

Cells

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“…In recent years, new coating technology has been actively pursued to improve the targeting effectiveness of pH-dependent delivery systems. For example, ColoPulse technology is an innovative pH responsive coating technology, which incorporates super-disintegrant in the coating matrix to accelerate the disintegration at the target site [50][51][52]. The incorporation of a super-disintegrant in a non-percolating mode leads to a more reliable and pulsatile drug release.…”

Section: Tablets and Capsulesmentioning

confidence: 99%

“…Furthermore, food and time of food intake did not affect the targeting effectiveness of ColoPulse delivery systems [51]. Recently, Gareb et al [52] adopted this technology to develop the ileo-colonic-targeted zero-order sustained-release tablets of budesonide for the topical treatment of IBD. The results indicated that drug release from the developed tablet began in the simulated ileum, and the release rate remained constant throughout the entire simulated colon [52].…”

Section: Tablets and Capsulesmentioning

confidence: 99%

“…Recently, Gareb et al [52] adopted this technology to develop the ileo-colonic-targeted zero-order sustained-release tablets of budesonide for the topical treatment of IBD. The results indicated that drug release from the developed tablet began in the simulated ileum, and the release rate remained constant throughout the entire simulated colon [52]. They also developed and validated the production process of oral infliximab tablet coated with ColoPulse technology for the local treatment of ileo-colonic IBD [53].…”

Section: Tablets and Capsulesmentioning

confidence: 99%

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Strategic Approaches for Colon Targeted Drug Delivery: An Overview of Recent Advancements

et al. 2020

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Colon targeted drug delivery systems have gained a great deal of attention as potential carriers for the local treatment of colonic diseases with reduced systemic side effects and also for the enhanced oral delivery of various therapeutics vulnerable to acidic and enzymatic degradation in the upper gastrointestinal tract. In recent years, the global pharmaceutical market for biologics has grown, and increasing demand for a more patient-friendly drug administration system highlights the importance of colonic drug delivery as a noninvasive delivery approach for macromolecules. Colon-targeted drug delivery systems for macromolecules can provide therapeutic benefits including better patient compliance (because they are pain-free and can be self-administered) and lower costs. Therefore, to achieve more efficient colonic drug delivery for local or systemic drug effects, various strategies have been explored including pH-dependent systems, enzyme-triggered systems, receptor-mediated systems, and magnetically-driven systems. In this review, recent advancements in various approaches for designing colon targeted drug delivery systems and their pharmaceutical applications are covered with a particular emphasis on formulation technologies.

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“…The use of conventional drug delivery systems in IBD is limited, since they lead to systemic absorption of the drug, with related side effects and toxicity [4], such as osteoporosis and osteonecrosis, adrenal suppression, diabetes, cataract and glaucoma, as well as gastro-intestinal, cutaneous and cardiovascular complications [5]. As a consequence, several innovative drug delivery systems have been developed to achieve a selective drug delivery to the inflamed tissues [6][7][8][9]. With this aim, several approaches can be followed, i.e., the use of prodrugs becoming active after the hydrolysis by specific colon enzymes [10], bioadhesive delivery systems [11], timed-dependent delivery systems [12] and drug coating with pH dependent polymers [13,14].…”

Section: Introductionmentioning

confidence: 99%

Pectin and Zinc Alginate: The Right Inner/Outer Polymer Combination for Core-Shell Drug Delivery Systems

et al. 2020

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Core-shell beads loaded with betamethasone were developed using co-axial prilling as production technique and pectin plus alginate as polymeric carriers. During this study, many operative conditions were intensively investigated to find the best ones necessary to produce uniform core-shell particle systems in a reproducible way. Particularly, feed solutions’ composition, polymers mass ratios and the effect of the main process parameters on particles production, micromeritics, inner structure, drug loading and drug-release/swelling profiles in simulated biological fluids were studied. The optimized core-shell formulation F5 produced with a pectin core concentration of 4.0% w/v and an alginate shell concentration of 2.0% w/v (2:1 core:shell ratio) acted as a sustained drug delivery system. It was able to reduce the early release of the drug in the upper part of the gastro-intestinal tract for the presence of the zinc-alginate gastro-resistant outer layer and to specifically deliver it in the colon, thanks to the selectivity of amidated low methoxy pectin core for this district. Therefore, these particles may be proposed as colon targeted drug delivery systems useful for inflammatory bowel disease (IBD) therapy.

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Development of novel zero-order release budesonide tablets for the treatment of ileo-colonic inflammatory bowel disease and comparison with formulations currently used in clinical practice

Abstract: Development of novel zero-order release budesonide tablets for the treatment of ileo-colonic inflammatory bowel disease and comparison with formulations currently used in clinical practice.

Cited by 25 publications

References 42 publications

Pirfenidone Inhibits Cell Proliferation and Collagen I Production of Primary Human Intestinal Fibroblasts

Pirfenidone Inhibits Cell Proliferation and Collagen I Production of Primary Human Intestinal Fibroblasts

Strategic Approaches for Colon Targeted Drug Delivery: An Overview of Recent Advancements

Pectin and Zinc Alginate: The Right Inner/Outer Polymer Combination for Core-Shell Drug Delivery Systems

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