In vitro and in vivo evaluation of a pH-, microbiota- and time-based oral delivery platform for colonic release.

Several formulation strategies have been proposed for oral colon delivery, particularly for the therapy of inflammatory bowel disease (IBD). However, targeting the large intestine remains a challenging goal. The aim of this study was to develop and evaluate a novel type of drug delivery system, which is based on multiple drug release triggers for reliable performance. The system consists of: (i) a drug core, (ii) an inner swellable low-viscosity hydroxypropyl methylcellulose (HPMC) layer, and (iii) an outer film coating based on a Eudragit® S:high-methoxyl (HM) pectin (7:3 w/w) blend, optionally containing chitosan. Convex immediate release tablets (2 or 4 mm in diameter) containing paracetamol or 5-aminosalicylic acid (5-ASA) were coated in a fluid bed. The double-coated tablets exhibited pulsatile release profiles when changing the release medium from 0.1 N HCl to phosphate buffer pH 7.4. Also, drug release was faster in simulated colonic fluid (SCF) in the presence of fecal bacteria from IBD patients compared to control culture medium from tablets with outer Eudragit® S: HM pectin: chitosan coatings. The latter systems showed promising results in the control of the progression of colitis and alteration of the microbiota in a preliminary rat study.

New formulation and delivery method of Cryphonectria parasitica for biological control of chestnut blight.

AIMS: This study aimed to develop a new formulation of Cryphonectria parasitica hypovirulent mycelium suitable for inoculations of tall trees from the ground. Cryphonectria parasitica hypovirulent strains are widely used for biological control of chestnut blight. However, it is often inconsistent and ineffective not only for biological reasons but also because the current manual application of hypovirulent strains on adult plants is difficult, time-consuming and expensive. Here, we propose an improved formulation and more effective mode of application of hypovirulent strains, which could boost chestnut blight biocontrol. METHODS AND RESULTS: The Cp 4.2H hypovirulent strain was formulated as mycelium discs with polyethylene glycol and hydroxypropyl methylcellulose, loaded into lead-free pellets that are used as carriers to inoculate cankers on chestnut stems by shooting. The formulation of mycelium did not hamper its viability which was stable, with an estimated shelf life of 72 days at 6 ± 1°C. The inoculum effectiveness was confirmed ex planta and in planta in a small-scale pilot study in field, where formulated mycelium discs of hypovirulent strain Cp 4.2H were inoculated by airgun shot method into the chestnut bark. In planta, Cp 4.2H was recovered in 37% of bark samples taken around the inoculated points 1 year after the treatment. CONCLUSIONS: We demonstrated that the proposed airgun shooting inoculation method of C. parasitica hypovirulent strain formulated as mycelium discs is suitable for treatment of adult chestnut trees. SIGNIFICANCE AND IMPACT OF THE STUDY: The proposed method could be a valid alternative to the traditional manual technique of chestnut biocontrol. The main advantages are the cost-effectiveness and the ease to treat high-positioned, otherwise unreachable cankers both in orchards and forests.