Interaction of Celecoxib with Membranes: The Role of Membrane Biophysics on its Therapeutic and Toxic Effects

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Catarina Pereira Leite (Author) Other; Claudia Nunes (Author) Other; Jose L F C Lima (Author) FFUP; Salette Reis (Author) FFUP; Marlene Lucio (Author) FFUP

Journal

Title: Journal of Physical Chemistry B

Vol. 116 No. 6

Pages: 13608-13617

ISSN: 1520-6106

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 24 Citations

Scopus - 33 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-002-3AT

DOI: 10.1021/jp304037v

Abstract (EN): The present work provides a biophysical characterization of the interaction of celecoxib, a cyclooxigenase-2 selective non-steroidal anti-inflammatory drug, with membranes using liposomes, constituted by phosphatidylcholines, as membrane model systems. In order to mimic biological conditions, the experiments were performed at physiological pH (7.4); at an acidic pH to mimic the conditions of the inflamed cells (5.0); and at different membrane physical states (gel, ripple, and fluid phase). Important information regarding the celecoxib-membrane interactions was gathered by the complementary biophysical techniques: derivative spectrophotometry was used to determine liposome/water partition coefficient of celecoxib; dynamic light scattering (DLS) measurements to study the influence of celecoxib on lipid main phase transition temperature; fluorescence binding measurements were made to assess the location of celecoxib within the membrane; and small-angle and wide-angle X-ray scattering (SAXS and WAXS) were used to assess the changes in the structure and order of phosphatidylcholine bilayers caused by the presence of celecoxib. The overall results obtained indicate that celecoxib greatly interacts with membranes. Briefly, celecoxib exhibits a high liposome/water partition coefficient that is non-pH-dependent, but the location of celecoxib within the membrane is pH-dependent. In fact, celecoxib is more deeply located inside the membrane at pH 5.0, while it locates closer to the surface at pH 7.4. DLS, SAXS, and WAXS results have shown a high membrane fluidization in the presence of celecoxib, especially at pH 7.4. Overall, the Current study can contribute to a biophysical characterization of the celecoxib-membrane interaction. The relevance of the gathered results will be discussed in terms of the reported celecoxib therapeutic and toxic effects.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10