Interaction of celecoxib with membranes: the role of membrane biophysics on its therapeutic and toxic effects.

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  • Author(s): Pereira-Leite C;Pereira-Leite C; Nunes C; Lima JL; Reis S; Lúcio M
  • Source:
    The journal of physical chemistry. B [J Phys Chem B] 2012 Nov 26; Vol. 116 (46), pp. 13608-17. Date of Electronic Publication: 2012 Nov 09.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: American Chemical Society Country of Publication: United States NLM ID: 101157530 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-5207 (Electronic) Linking ISSN: 15205207 NLM ISO Abbreviation: J Phys Chem B Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, D.C. : American Chemical Society, c1997-
    • Subject Terms:
      Biophysics*; Cell Membrane/*drug effects ; Lipid Bilayers/*chemistry ; Liposomes/*chemistry ; Pyrazoles/*chemistry ; Sulfonamides/*chemistry; Anti-Inflammatory Agents, Non-Steroidal/chemistry ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Anti-Inflammatory Agents, Non-Steroidal/toxicity ; Celecoxib ; Models, Molecular ; Pyrazoles/pharmacology ; Pyrazoles/toxicity ; Sulfonamides/pharmacology ; Sulfonamides/toxicity
    • Abstract:
      The present work provides a biophysical characterization of the interaction of celecoxib, a cyclo-oxigenase-2 selective nonsteroidal 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 were performed 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.
    • Accession Number:
      0 (Anti-Inflammatory Agents, Non-Steroidal)
      0 (Lipid Bilayers)
      0 (Liposomes)
      0 (Pyrazoles)
      0 (Sulfonamides)
      JCX84Q7J1L (Celecoxib)
    • Publication Date:
      Date Created: 20121026 Date Completed: 20130506 Latest Revision: 20151119
    • Publication Date:
      20240829
    • Accession Number:
      10.1021/jp304037v
    • Accession Number:
      23094761