Bust the gut: novel drug delivery method targets the colon to treat IBD
By coating a capsule with a polymer that can be broken down by gut microbes, a team of scientists has developed a new targeted oral infliximab treatment for people with inflammatory bowel disease (IBD).
A research collaboration between deep tech innovation organisation, CPI (Redcar, UK), and pharma companies Intract Pharma (London, UK), SGS Quay Pharma (Deeside, UK) and Pharmidex (London, UK), has repackaged the IBD monoclonal antibody (mAb) treatment, infliximab, into an oral capsule for the first time. Not only is this delivery method life-changing for patients, but the novel formulation ensures the drug is more targeted, thereby reducing the risk of immunosuppression.
IBDs are very distressing illnesses, with Crohn’s disease and ulcerative colitis being the two most common forms. Over 3 million people in the USA are estimated to have a form of IBD, for which there is currently no cure. Those with IBD can keep their symptoms at bay with biotherapeutics; however, these are delivered via IV infusion or injection in hospital, which can cause adverse side effects.
Developing delivery systems for getting drugs to the colon – the target for IBD – is challenging. “Protein-based therapeutics are generally unstable in the harsh conditions of the gut and rapidly degrade before being able to exert any effect,” explains Silvia Matiz, formulation scientist at Intract.
The team, therefore, set out to develop a novel oral delivery system for infliximab that could survive the harsh conditions of the gut. To do this, infliximab was combined with a novel ‘enhancer’ technology in the capsule’s core, which protects infliximab from enzymatic degradation once released into the gastrointestinal environment and enhances its uptake by the colon, ensuring a site-specific therapeutic effect.
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To further protect the mAb, the team coated the capsule with Intract’s Phloral® technology, a combination of a pH- and bacteria-responsive polymers. The bacteria responsive polymer is broken down by the specific bacterial profile in the colonic microbiome, while the alteration in pH from the small intestine to the colon leads to the breakdown of the pH-responsive polymer.
Not only would this new infliximab capsule reduce the risk of immunosuppression by being more targeted, but it would also enable patients to take their IBD treatment in the comfort of their own home, reducing associated patient distress, as well as costs for healthcare systems.
Intract is hoping to move forward with clinical trials in 2023, and if these are successful the infliximab capsule would become the first commercially available oral mAb therapy. In the future, Intract is aiming to use its technologies for other applications, including infectious diseases of the colon, neurological disorders via the gut-brain axis targeting, autoimmune diseases via the gut-immune axis targeting, and vaccine delivery for mucosal and systemic immunity through mRNA delivery to gut epithelial cells.
