Drug delivery firm aims to solve NSAID problems

With COX-2 inhibitors falling out of favour, the temptation might be to prescribe older non-steroidal anti-inflammatory drugs, but these have their own problems, including a greater tendency to cause gastrointestinal side effects.

Earlier this week, a study published in the journal Clinical Gastroenterology and Hepatology (January 18) suggested that the incidence of GI side effects with these older NSAIDs was higher than had been thought, affecting 71 per cent of patients taking NSAIDs compared to just 10 per cent among those taking the unrelated painkiller acetaminophen (also known as paracetamol).

One solution could be to use drug delivery technologies to limit the damage caused by older NSAIDs, and reduce the need for the concomitant use of other drugs - such as the prostaglandin misoprostol, H2 antagonists or proton pump inhibitors - to protect the GI tract.

BioDelivery Sciences International reported yesterday the results of laboratory tests that suggest that its Bioral 'nanocochleate' drug delivery technology can achieve just that.

The company has tested Bioral formulations of aspirin and other NSAIDs in a well-established animal model of inflammation and demonstrated that encochleated NSAIDS enabled a statistically significant reduction in GI toxicity compared to standard formulations at clinically-relevant high doses of these NSAIDs and aspirin while providing comparable anti-inflammatory effects.

The Bioral technology uses soy-derived phospholipid and calcium to envelope the drug in such a way that it appears to allow absorption to occur without the NSAID coming into contact with the gastric mucosa, thus reducing the incidence of mucosal ulceration that is often associated with NSAID and aspirin use.

That said, various modified-release approaches have been applied to NSAIDs, from simple enteric coatings to more sophisticated sustained release technologies, with little success. One consequence has been to shift the site of GI inflammation from the stomach to the small intestine, where damage can remain asymptomatic until more serious problems arise.

There are believed to be two ways in which NSAIDs cause damage to the GI mucosa. One is a topical effect: many NSAIDs are ionised when they enter cells, causing localised damage. It is this local action that BDSI hopes to overcome with its delivery technology.

However, the other mechanism is intrinsically related to the mechanism of action of NSAIDs in blocking COX, the rate-limiting enzyme in prostaglandin synthesis. Prostaglandins are intimately involved in inflammation and pain recognition, but are also a fundamental part of the mechanism that protects the gastric mucosa from the contents of the gut. So drug delivery is unlikely to solve this element of NSAID toxicity.

That said, BDSI is hopeful that its technology could improve matters in a manner similar to the COX-2 inhibitors, which attempted to block only the element of the COX pathway involved in inflammation and leave the protective mechanisms intact.

"The major alleged benefit of the selective COX-2 inhibitors over the NSAIDs has been reduced gastrointestinal damage. However, the new laboratory findings show that it may be possible for this benefit to now be matched by applying the Bioral technology to NSAIDs and aspirin,"​ said the company in a statement.