Development of the PC-NSAID technology: From contact angle to Vazalore

• Published in: Drug discovery today Vol. 28; no. 1; p. 103411
• Main Author: Lichtenberger, Lenard M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2023
• Subjects: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; COX; cyclo-oxygenase; Gastrointestinal Diseases; Humans; hydrophobicity; ibuprofen; inflammation; nonsteroidal anti-inflammatory drugs; phosphatidylcholine; Phosphatidylcholines - chemistry; phospholipids; Platelet; ulcer; nonsteroidal anti-inflammatory drugs; hydrophobicity; Platelet; inflammation; phosphatidylcholine; aspirin; ibuprofen; cyclo-oxygenase; ulcer; phospholipids; COX
• ISSN: 1359-6446; 1878-5832; 1878-5832
• DOI: 10.1016/j.drudis.2022.103411

•The gastric mucosa has non-wettable, hydrophobic properties.•The hydrophobic property of the gastric mucosa is attributable to an extracellular lining of surface-active phospholipids.•NSAIDs disrupt the hydrophobic surface properties of the stomach by associating with the phospholipid lining of the tissue surface.•Pre-association of NSAIDs with phosphatidylcholine reduces the drug’s GI toxicity without affecting its therapeutic activity.•Aspirin-PC (Vazalore®) maintained full anti-platelet activity when compared to aspirin that was not associated with phosphatidylcholine. We describe strategies in drug development to reduce the gastrointestinal (GI) toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs). We then provide an overview of the experiments that led to the development of PC-NSAIDs, a novel family of NSAIDs associated with phosphatidylcholine (PC) that have reduced GI toxicity and full therapeutic activity. Furthermore, we describe the evidence showing: that the stomach possesses hydrophobic properties that are attributable to phospholipids lining the mucus gel layer; and that NSAIDs chemically associate with intrinsic PC, thereby attenuating the tissue’s hydrophobic properties. Further, pre-associating NSAIDs with PC reduces the GI toxicity of these drugs, both in rodent ulcer models and in human subjects, without affecting the drugs’ therapeutic activity. Finally, we discuss the commercialization and launch of Aspirin-PC, an over-the-counter (OTC) drug with the brand name Vazalore®.