title: NSAIDs interactions with membranes: a biophysical approach.
abstract: This work focuses on the interaction of four representative NSAIDs (nimesulide, indomethacin, meloxicam, and piroxicam) with different membrane models (liposomes, monolayers, and supported lipid bilayers), at different pH values, that mimic the pH conditions of normal (pH 7.4) and inflamed cells (pH 5.0). All models are composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) which is a representative phospholipid of most cellular membranes. Several biophysical techniques were employed: Fluorescence steady-state anisotropy to study the effects of NSAIDs in membrane microviscosity and thus to assess the main phase transition of DPPC, surface pressure-area isotherms to evaluate the adsorption and penetration of NSAIDs into the membrane, IRRAS to acquire structural information of DPPC monolayers upon interaction with the drugs, and AFM to study the changes in surface topography of the lipid bilayers caused by the interaction with NSAIDs. The NSAIDs show pronounced interactions with the lipid membranes at both physiological and inflammatory conditions. Liposomes, monolayers, and supported lipid bilayers experiments allow the conclusion that the pH of the medium is an essential parameter when evaluating drug-membrane interactions, because it conditions the structure of the membrane and the ionization state of NSAIDs, thereby influencing the interactions between these drugs and the lipid membranes. The applied models and techniques provided detailed information about different aspects of the drug-membrane interaction offering valuable information to understand the effect of these drugs on their target membrane-associated enzymes and their side effects at the gastrointestinal level.
authors.affiliation: REQUIMTE, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha, Porto, Portugal.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Nunes
authors.forename: Gerald
authors.initials: G
authors.lastname: Brezesinski
authors.forename: Catarina
authors.initials: C
authors.lastname: Pereira-Leite
authors.forename: José L F C
authors.initials: JL
authors.lastname: Lima
authors.forename: Salette
authors.initials: S
authors.lastname: Reis
authors.forename: Marlene
authors.initials: M
authors.lastname: Lúcio
mesh_terms: D016880:Anisotropy; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D005454:Fluorescence Polarization / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D015394:Molecular Structure
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008051:Lipid Bilayers; D008081:Liposomes