PC-NSAIDs: Gastrointestinal-safe and potent anti-inflammatory drugs

We have developed a novel class of phosphatidylcholine (PC)-associated nonsteroidal antiinflammatory drugs (NSAIDs) to treat inflammation and pain with reduced GI side-effects. In Phase I studies using a number of in vitro systems monitoring the activity and threshold of nociceptive fibers under basal conditions and after exposure to inflammatory mediators, we demonstrated that a number of PC-NSAIDs were more effective than the unmodified drugs in reducing the activity of pain sensory nerves. Interestingly, preliminary analysis of in vitro primary human osteoblasts suggest that PC-NSAIDs may have favorable effects on bone remodeling compared with unmodified NSAIDs Based upon these studies, we propose to investigate in Phase II the therapeutic actions of the most effective PC-NSAID we have identified, Indomethacin-PC (vs. unmodified indomethacin) in rodent models of joint and nerve inflammation, post-operative incisional pain (to both mechanical and thermal stimulation) and bone healing. We also propose to evaluate the GI toxicity of the test NSAIDs in the above in vivo model systems to confirm Indomethacin-PC’s superior GI safety. The parenteral and oral formulations of Indomethacin-PC will be optimized by the scientists at PLx Pharma in close consultation with our industrial advisors and our Co-investigators at the two University of Texas institutions.