Oral drug delivery of therapeutic gases - carbon monoxide release for gastrointestinal diseases.

Deploying the therapeutic potential of carbon monoxide (CO) in various gastrointestinal diseases is challenged by inappropriate oral delivery modes. It is for this challenge, that we developed an easy to use tablet referred to as oral carbon monoxide release system (OCORS) providing precise, controlled, tunable and targeted CO delivery for the treatment of sequelae of gastrointestinal diseases. OCORS is an oral tablet based on sulfite induced CO release from the CO releasing molecule 2 (CORM-2). OCORS performance was detailed as a function of the presence of buffer within the tablet core and the composition of a semipermeable cellulose acetate coating, shielding the tablet core. OCORS delivered CO for up to 10h with a nearly linear release profile between approximately 30 to 240min. This controlled release system delivered the therapeutic gas independent of environmental pH for reliable CO generation at gastric, intestinal or colonic sites. In vivo experiments and toxicological assessments particularly with respect to observed ruthenium release of OCORS are required to demonstrate the pharmacokinetics and clinical potential of this oral delivery platform for therapeutic gases.