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

Contrasting in vitro and in vivo systems will be used to evaluate the anti-inflammatory/analgesic activity and side-effects of a family of phosphatidylcholine (PC) – associated NSAIDs. Previous studies indicate that PC-NSAIDs have equivalent and/or enhanced therapeutic activity while GI ulceration/bleeding is remarkably reduced. Dr. Susan Carlton’s lab will measure the effect of our test NSAIDs (PC-NSAID vs unmodified NSAIDs) on calcium signaling of rodent dorsal root ganglia cells in response inflammatory mediators. Her lab also will electrophysiologically measure the effect of test NSAIDs on nociceptive C-fiber activity of a rodent skin-nerve preparation. Dr. Catherine Ambrose will investigate the effect of the test NSAIDs on growth/apoptosis of human osteoblasts in culture. During the Option period, Dr. Lenard Lichtenberger’s lab will utilize a rodent model of adjuvant-induced joint inflammation that provides information on the anti-inflammatory/analgesic activity of the test NSAIDs and their ability to induce GI ulceration/bleeding. The synovial fluid eicosanoids will be measured by HPLC/MS. Dr. Carlton also will evaluate the anti-inflammatory/analgesic activity of PC-NSAIDs using a rodent hindlimb incision model. In Phase II we plan to expand our in vivo evaluation of PC-NSAIDs using an array of rodent model systems available in the labs of the Co-Investigators.