Can NO-indomethacin counteract the topical gastric toxicity induced by indomethacin interactions with phospholipid bilayers?

Publication date: 1 September 2018 Source:Colloids and Surfaces B: Biointerfaces, Volume 169 Author(s): Catarina Pereira-Leite, Cláudia Nunes, José C. Bozelli, Shirley Schreier, Christina S. Kamma-Lorger, Iolanda M. Cuccovia, Salette Reis Nitric oxide (NO)-releasing nonsteroidal anti-inflammatory drugs (NSAIDs) have been developed to overcome the gastrointestinal and cardiovascular toxicity of NSAIDs, by chemically associating a NO-releasing moiety with commercial NSAIDs. Since increasing evidence supports that NSAIDs toxicity is related to their topical actions in membrane lipids, this work aims to evaluate the impact of adding a NO-releasing moiety to parent NSAIDs regarding their effect on lipid bilayers. Thus, the interactions of NO-indomethacin and indomethacin (parent drug) with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers were described herein at pH 3.0 and 7.4. Diverse experimental techniques were combined to characterize the partitioning and location of drugs in DMPC bilayers, and to analyze their effect on the lipid phase transition and the bilayer structure and dynamics. The partitioning of NO-indomethacin into DMPC bilayers was similar to that of charged indomethacin and smaller than that of neutral indomethacin. Both drugs were found to insert the DMPC bilayer and the membrane location of indomethacin was pH-dependent. NO-indomethacin and indomethacin induced a decrease of the main phase transition temperature of DMPC. The effect of thes...
Source: Colloids and Surfaces B: Biointerfaces - Category: Biochemistry Source Type: research