Effects of non-steroidal anti-inflammatory drugs on the structure of lipid bilayers: therapeutical aspects

• Type: Article in International Scientific Journal
• Date: 2011

Authors

Claudia Nunes (Author) Other; Gerald Brezesinski (Author) Other; Jose L F C Lima (Author) FFUP; Salette Reis (Author) FFUP; Marlene Lucio (Author) FEUP

Journal

Title: Soft Matter

Vol. 7 No. 1

Pages: 3002-3010

ISSN: 1744-683X

Publisher: Royal Society of Chemistry

Indexing

ISI Web of Knowledge - 21 Citations

Scopus - 25 Citations

Scientific classification

FOS: Engineering and technology > Materials engineering

CORDIS: Physical sciences > Chemistry > Analytical chemistry

Other information

Authenticus ID: P-002-ZJC

DOI: 10.1039/c0sm00686f

Resumo (PT): Inflammatory processes are phenomena that initiate at the cellular surface. Therefore, the study of interactions of non-steroidal anti-inflammatory drugs (NSAIDs) with membranes or model membranes is a fundamental step for the enlightenment of their pharmacological activity. Despite their similar chemical structures, NSAIDs have different biological impact, concerning their therapeutic effects. The mechanisms leading to these differences may be related to their different effects on the structural parameters of lipid bilayers. In this study, the molecular interaction between five NSAIDs (piroxicam, meloxicam, tolmetin, indomethacin and nimesulide), widely used in the clinical practice, and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) as a membrane model was investigated by small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS). The present study provides evidence that NSAIDs produce distinct biophysical effects depending on the initial organization of the membrane. All the NSAIDs studied reduce or abolish the pre-transition temperature (Lβ′ → Pβ′) indicating a surface-disordering effect of these drugs. The main lipid phase transition (Pβ′ → Lα) is also affected by the NSAIDs studied, with the exception of nimesulide. Meloxicam, tolmetin and indomethacin have the major effects on the Lα phase structure of the DPPC bilayers, which can also be related to their enhanced therapeutic effect as anti-inflammatory drugs. The structural disorder effects found for the NSAIDs studied in the Lβ′ phase of the bilayers follow the order: meloxicam > indomethacin > tolmetin > piroxicam and can be also correlated with the anti-oxidant effect of these NSAIDs. <br> <br>

Abstract (EN): Inflammatory processes are phenomena that initiate at the cellular surface. Therefore, the study of interactions of non-steroidal anti-inflammatory drugs (NSAIDs) with membranes or model membranes is a fundamental step for the enlightenment of their pharmacological activity. Despite their similar chemical structures, NSAIDs have different biological impact, concerning their therapeutic effects. The mechanisms leading to these differences may be related to their different effects on the structural parameters of lipid bilayers. In this study, the molecular interaction between five NSAIDs (piroxicam, meloxicam, tolmetin, indomethacin and nimesulide), widely used in the clinical practice, and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) as a membrane model was investigated by small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS). The present study provides evidence that NSAIDs produce distinct biophysical effects depending on the initial organization of the membrane. All the NSAIDs studied reduce or abolish the pre-transition temperature (L(beta') -> P(beta')) indicating a surface-disordering effect of these drugs. The main lipid phase transition (P(beta') -> L(alpha)) is also affected by the NSAIDs studied, with the exception of nimesulide. Meloxicam, tolmetin and indomethacin have the major effects on the L(alpha) phase structure of the DPPC bilayers, which can also be related to their enhanced therapeutic effect as anti-inflammatory drugs. The structural disorder effects found for the NSAIDs studied in the L(beta') phase of the bilayers follow the order: meloxicam > indomethacin > tolmetin > piroxicam and can be also correlated with the antioxidant effect of these NSAIDs.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9