Development of solution Based on Natural Polymers in Order to Reduce the Therapeutic Doses of Current Treatments and Their Adverse Effects in Chronic Inflammatory Bowel Diseases (IBD)

International audienc

Valorisation de la pulpe de fruit de baobab comme nouvel excipient pharmaceutique : aspect biologique et biopharmaceutique

The oral administration of therapeutic proteins and live biotherapeutics products presents a challenge for the pharmaceutical industry. The aim of this work is to explore the potential of baobab fruit pulp from Andansonia digitata (BB) as a new excipient with interesting biological and functional properties.In the first part of this work, the biological properties of BB (anti-inflammatory, antioxidant, healing, regulation of intestinal permeability, analgesic) were demonstrated in vitro, ex vivo and in vivo. BB seems to be a good candidate for the treatment or prevention of chronic inflammatory bowel diseases, IBD.In a second part, the functional properties of BB associated with whey proteins (WP) and alginate (ALG) were evaluated. BB is of interest in hydrogel formulation obtained by ionotropic gelation because of its excellent gelation and mucoadhesion properties. A microparticulate formulation (MP) has been successfully performed and allows gastroresistance and controlled release of a model active substance (AS). BB allows for the formation of a strong gel, with decreased mesh size of the network and reduced swelling of the MP. In a tablet formulation, the addition of BB improves the manufacturing process of tablets prepared by direct compression. The resulting matrix tablets provide prolonged release regardless of pH. The addition of enzymes in the artificial digestive system accelerates the erosion of the tablet but the release of AS remains prolonged for 4 h. Combining the obtained release profile and the mucoadhesive behavior of BB associated with WP/ALG, BB powders can be considered as a novel excipient for sustained release applications.L’administration orale des protéines thérapeutiques et de produits biothérapeutiques vivants présente un défi pour l’industrie pharmaceutique. Le but de ce travail est d’explorer les potentialités de la pulpe de fruit de baobab d’Andansonia digitata (BB) comme nouvel excipient possédant des propriétés biologiques et fonctionnelles intéressantes.Dans la première partie de ce travail, les propriétés biologiques du BB (anti-inflammatoire, antioxydante, cicatrisante, régulation de la perméabilité intestinale, analgésique) ont été démontrées in vitro, ex vivo et in vivo. Le BB semble être un bon candidat pour le traitement ou la prévention des maladies inflammatoires chroniques de l’intestin, les MICI.Dans une deuxième partie, les propriétés fonctionnelles du BB, associé aux protéines de lactosérum (PL) et à l’alginate (ALG), ont été évaluées. Le BB présente un intérêt dans la formulation d’hydrogel obtenu par gélification ionotropique en raison de ses excellentes propriétés de gélification et de mucoadhésion. Une formulation microparticulaire (MP) a été réalisée avec succès et permet une gastrorésistance et une libération contrôlée d’une substance active (SA) modèle. LeBB permet la formation d’un gel fort, avec diminution de la taille des mailles du réseau et diminution du gonflement de la MP. Dans une formulation comprimé, l'ajout de BB améliore le process de fabrication des comprimés préparés par compression directe. Les comprimés matriciels obtenus assurent une libération prolongée quel que soit le pH. L’ajout d’enzymes dans le système digestif artificiel accélère l’érosion du comprimé mais la libération de la SA reste prolongée pendant 4 h.En combinant le profil de libération obtenu et le comportement mucoadhésif du BB associé aux PL/ALG, les poudres de BB peuvent être considérées comme un nouvel excipient pour les applications de libération prolongée

Rheological and mucoadhesion properties of vegetable extract with potential use in pharmaceutics as controlled release and bio-adhesive excipient in inflammatory bowel disease

International audienc

Nutritional approach to restore impaired intestinal barrier function and inflammatory after inflammation induction in cells and mice models

International audiencePurpose : Inflammatory bowel disease (IBD) is characterized by inflammation and permeability increased of the intestinal wall leading to diarrhea, abdominal pain, weight loss, eg. Various treatments nowadays allow patients to treat symptomatic attacks and to a lesser extent, to space them out. These treatments are effective but remain burdensome for the patients with numerous undesirable effects and considerably alter their quality of life. Our new vegetable extract (NE) based on natural anti-inflammatory polymers has been developed as nutritional formulation in order to improve benefit/risk ratio, and thus reduce the use of current treatments to preserve the quality of life and mobility of IBD patients. Aims of this work were 1/ to assess the toxicity and inflammatory response of NE (pathway and responsible composition) on cells culture and mice models and 2/ to determine the implication of NE in intestinal permeability and membrane integrity.NE composition has been studied (flavonoids, vitamin C, polyphenol…) by chemical dosages and evaluated on cellular metabolism in vitro. The different types of inflammatory mediators (inflammatory cytokines) were determined by ELISA assay, and the treatment action on NF-kB pathway was determined after induction of inflammation by lipopolysaccharides (LPS) on Raw 264.7 cells by western blot. The proof of concept was evaluated in vivo on Fvb/n mice models treated with DSS representative of IBD pathologies. Secondly, the modification of permeability (in vitro and ex vivo) in IBD context was evaluated with NE treatment.The efficacy of the in vitro and in vivo treatments shows a decrease in inflammatory factors and inhibition of NF-kB pathway as well as a reduction of the digestive permeability system, particularly at the colonic level. The formulation of a nutritional vector based on natural excipient NE could be an effective therapeutic solution to treat IBD

Microparticles encapsulation of vegetable extract with potential use in pharmaceutics as controlled release and bio-adhesive excipient in inflammatory bowel disease

International audienc

Effect of baobab pulp powder on controlled release properties of matrix tablet formulated with whey protein and alginate

International audienc

Development of a vector based on natural excipient in order to reduce the therapeutic doses of current treatments and their adverse effects in chronic inflammatory bowel diseases (IBD).

International audienc