Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications in the world because of their high efficiency in reducing pain and inflammation [1]. The basic mode of their action is inhibition of the pro-inflammatory membrane enzyme cyclooxygenase (COX) [2]. Some highly potent of NSAIDs belong to the oxicam group: meloxicam (MEL), piroxicam (PIR), and tenoxicam (TEN); these drugs have different biological effects despite their similar chemical structures. Because the prerequisite for accessing the cyclooxygenase by the drugs is interaction with the membrane, the focus of the current study was a comparison of how MEL, PIR, and TEN interact with model biological membranes.

In this research, model membranes formed with different phosphoglycerides were studied using Langmuir technique upon interaction with TEN, PIR, and MEL. Changes of the phospholipid monolayer properties induced by the oxicam drugs were studied with surface pressure and surface electrical potential, polarization modulation infrared reflection absorption spectra, Brewster angle microscopy and phospholipase A2 (PLA2) activity [3]. The monolayer experiments demonstrated significant differences between the interfacial properties of MEL, PIR and TEN. Indeed, the results obtained show that MEL has the highest ability to modify membrane fluidity and surface potential, followed by PIR and TEN. Additionally, the lipolysis experiments show that PLA2 activity is different upon interaction with the three drugs; it decrease more significantly in the presence of MEL compared to the other two oxicams. We suggest that the least polar MEL penetrates more easily to the film compared to PIR and TEN, and the effects observed are proportional to the amount of the oxicams present in the film. Moreover, the overall results indicate that the oxicams interact both with the apolar methylene and with the polar carbonyl groups; this leads us to think that the oxicams are localized between the lipid hydrocarbon chains and the polar heads in the monolayer. It can be expected that the capacity of the NSAIDs to penetrate into the lipid layer is crucial for accessing and inhibiting COX-2 and, consequently for the therapeutic efficiency of the three oxicams.

[1] C. K. S. Ong, P. Lirk, C. H. Tan, R. A. Seymour, Clin. Med. Res., 5, 19-34, 2007.

[2] J. R. Vane, Nature, New Biology, 231, 232-235, 1971.

[3] K. Wieclaw, B. Korchowiec, Y. Corvis, J. Korchowiec, H. Guermouche, E. Rogalska, Langmuir 25, 1417-1426, 2009.

Acknowledgments: This work is supported financially by the Ministry of Science and Higher Education, Grant No N N204 147537.

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