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Article Dans Une Revue International Journal of Pharmaceutics: X Année : 2024

Colon targeting in rats, dogs and IBD patients with species-independent film coatings

Résumé

Polysaccharides were identified, which allow for colon targeting in human Inflammatory Bowel Disease (IBD) patients, as well as in rats and dogs (which are frequently used as animals in preclinical studies). The polysaccharides are degraded by colonic enzymes (secreted by bacteria), triggering the onset of drug release at the target site. It has to be pointed out that the microbiota in rats, dogs and humans substantially differ. Thus, the performance of this type of colon targeting system observed in animals might not be predictive for patients. The aim of this study was to limit this risk. Different polysaccharides were exposed to culture medium inoculated with fecal samples from IBD patients, healthy dogs and “IBD rats” (in which colonic inflammation was induced). Dynamic changes in the pH of the culture medium were used as an indicator for the proliferation of the bacteria and, thus, the potential of the polysaccharides to serve as their substrate. Fundamental differences were observed with respect to the extent of the pH variations as well as their species-dependency. The most promising polysaccharides were used to prepare polymeric film coatings surrounding 5-aminosaliciylic acid (5-ASA)-loaded starter cores. To limit premature polysaccharide dissolution/swelling in the upper gastro intestinal tract, ethylcellulose was also included in the film coatings. Drug release was monitored upon exposure to culture medium inoculated with fecal samples from IBD patients, healthy dogs and “IBD rats”. For reasons of comparison, also 5-ASA release in pure culture medium was measured. Most film coatings showed highly species-dependent drug release kinetics or limited colon targeting capacity. Interestingly, extracts from aloe vera and reishi (a mushroom) showed a promising potential for colon targeting in all species.
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Dates et versions

hal-04504251 , version 1 (14-03-2024)

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Paternité - Pas d'utilisation commerciale - Pas de modification

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Fabiana Ferraro, Lisa Sonnleitner, Christel Neut, Séverine Mahieux, Jérémy Verin, et al.. Colon targeting in rats, dogs and IBD patients with species-independent film coatings. International Journal of Pharmaceutics: X, 2024, International Journal of Pharmaceutics: X, 7, pp.100233. ⟨10.1016/j.ijpx.2024.100233⟩. ⟨hal-04504251⟩

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