Skip to main content
SpringerLink
Log in

Partition and location of nimesulide in EPC liposomes: a spectrophotometric and fluorescence study

  • Special Issue Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Study of the mechanism of action of anti-inflammatory drugs (NSAIDs) and their side-effects may fall in the domain of membranology. In this work the extent of the interaction between an NSAID (nimesulide) and membrane phospholipids was quantified by the partition coefficient, K p , using egg phosphatidylcholine (EPC) liposomes as cell membrane models. The liposome/aqueous phase partition coefficients were determined under physiological conditions, by derivative spectrophotometry and fluorescence quenching. Derivative spectrophotometry allows elimination of background signal effects (light scattering) due to the presence of liposomes. Theoretical models, accounting for simple partition of the NSAID between two different media, were used to fit the experimental data, allowing the determination of K p in multilamellar vesicles (MLVs) and large unilamellar vesicles (LUVs). The location of nimesulide in MLVs and LUVs was evaluated by fluorescence quenching using spectroscopic probes located at different sites on the membrane. All n-AS probes were quenched and the relative quenching efficiencies were ordered as 2-AS<6-AS≈9-AS<12-AS; this suggests the drug is deeply buried in the membrane. Fluorescence quenching using the 12-AS probe was also used to determine the partition coefficient of the drug in MLVs and LUVs. The two techniques yield similar results. Finally, measurement of zeta-potential in the presence of different concentrations of nimesulide was performed to investigate possible changes in the zwitterionic phosphatidylcholine membranes. The membrane surface potential was not altered, which seems to be an indication that nimesulide binds to lipid bilayer mostly by hydrophobic interactions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.

Similar content being viewed by others

References

  1. Barrier CH, Hirschowitz BI (1989) Arthritis Rheum 32:926–929

    CAS  PubMed  Google Scholar 

  2. Vane JR (1971) Nature 231:232–235

    Google Scholar 

  3. Hla T, Neilson K (1992) Proc Natl Acad Sci USA 89:7384–7388

    CAS  PubMed  Google Scholar 

  4. Patrono C, Ciabattoni G, Patrignani P, Pugliese F, Filabuzzi P, Catella F, Davi G, Forni L (1985) Circulation 72:117–184

    Google Scholar 

  5. Tavares IA, Bishai PM, Bennett A (1995) Arzneimittelforschung 45:1093–1095

    CAS  PubMed  Google Scholar 

  6. Lichtenberger LM, Wang ZM, Romero JJ et al (1995) Nat Med 1:154–158

    CAS  PubMed  Google Scholar 

  7. Betageri GV, Rogers JA (1988) Int J Pharm 46:95–102

    Article  CAS  Google Scholar 

  8. Welti R, Mullikin LJ, Yoshimura T, Helmkamp GM Jr (1984) Biochemistry 23:6086–6091

    CAS  PubMed  Google Scholar 

  9. Kitamura K, Imayoshi N, Goto T, Shiro H, Mano T, Nakai Y (1995) Anal Chim Acta 304:101–106

    Article  CAS  Google Scholar 

  10. Kitamura K, Imayoshi N (1992) Anal Sci 8:497–501

    CAS  Google Scholar 

  11. Gürsoy A, Senyücel B (1997) J Microencapul 14:769–776

    Google Scholar 

  12. Lasic DD (1993) Liposomes—from physics to applications. Elsevier, New York

  13. McClare CWF (1971) Anal Biochem 9:527

    Google Scholar 

  14. New RRC (1990) Liposomes—a practical approach. Oxford University Press, New York

  15. Coutinho A, Prieto M (1993) J Chem Educ 70:425

    CAS  Google Scholar 

  16. Kiselev MA et al (1999) J Alloy Compd 286:195–202

    Article  CAS  Google Scholar 

  17. Wenk MR, Fahr A, Reszka R, Seelig J (1996) J Pharm Sci 85:228–231

    Article  CAS  PubMed  Google Scholar 

  18. White SH, Jacobs RE, King GI (1987) Biophys J 52:663

    CAS  PubMed  Google Scholar 

  19. Blatt E, Sawyer WH (1985) Biochim Biophys Acta 822:43

    Article  CAS  PubMed  Google Scholar 

  20. Cabrini G, Verkman AS (1986) Biochim Biophys Acta 862:285

    Article  CAS  PubMed  Google Scholar 

  21. Chalpin DB, Kleinfield AM (1983) Biochim Biophys Acta 731:465

    Article  CAS  Google Scholar 

  22. Fato R, Battino M, Esposti MD, Castelli GP, Lenaz G (1986) Biochemistry 25:3378

    CAS  PubMed  Google Scholar 

  23. Dupou-Cézanne L, Sautereau AM, Tocanne JF (1989) Eur J Biochem 181:695

    PubMed  Google Scholar 

  24. Haigh EA, Thulborn KR, Sawyer WH (1979) Biochemistry 18:3525

    CAS  PubMed  Google Scholar 

  25. Sikaris KA, Sawyer WH (1982) Biochem Pharmacol 31:2625

    Article  CAS  PubMed  Google Scholar 

  26. Vermeir M, Boens N (1992) Biochim Biophys Acta 1104:63

    Article  CAS  PubMed  Google Scholar 

  27. Blatt E, Ghiggino KP, Sawyer WH (1981) J Chem Soc, Faraday Trans 1 77:2551

  28. Putilina T, Sittenfeld D, Chader GJ, Wiggert B (1993) Biochemistry 32:3797

    CAS  PubMed  Google Scholar 

  29. Lacowicz JR (1999) Principles of Fluorescence Spectroscopy, 2nd edn. Kluwer, New York

  30. Gazzara JA, Phillips MC, Lund-Katz S, Palgunachari MN, Segrest JP, Anantharamaiah GM, Rodrigueza WV, Snow JW (1997) J Lipid Res 38:2147

    CAS  PubMed  Google Scholar 

  31. Matos C, Reis S et al (2001) Colloids Surf A 190:205–212

    Google Scholar 

  32. Thulborn KR, Sawyer WH (1978) Biochim Biophys Acta 511:125

    Article  CAS  PubMed  Google Scholar 

  33. Villalaín J, Prieto M (1991) Chem Phys Lipids 59:9

    Article  Google Scholar 

  34. Abrams FS, London E (1993) Biochemistry 32:10826

    CAS  PubMed  Google Scholar 

  35. Castro B, Gameiro P, Lima JLFC, Matos C, Reis S (2001) Lipids 36:89–96

    PubMed  Google Scholar 

  36. Thulborn KR, Tilley LM, Sawyer WH, Treloar FE (1979) Biochim Biophys Acta 558:166

    Article  CAS  PubMed  Google Scholar 

  37. Magni E (1991) Drug Invest 3(Suppl 2):1–3

Download references

Acknowledgements

Financial support for this work was provided by Fundação para a Ciência e Tecnologia (FCT) (Portugal), through the contract POCTI 34308/99. HF and ML thank FCT for the fellowships (BD6829/01) and (BD21667/99) respectively.

Author information

Authors and Affiliations

  1. REQUIMTE, Departamento de Química-Física, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha, 4050-047, Porto, Portugal

    Helena Ferreira, Marlene Lúcio, José L. F. C. Lima & Salette Reis

  2. REQUIMTE, Departamento de Química, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, 4050-039, Porto, Portugal

    Baltazar de Castro & Paula Gameiro

Authors
  1. Helena Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marlene Lúcio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Baltazar de Castro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paula Gameiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. José L. F. C. Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Salette Reis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Salette Reis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ferreira, H., Lúcio, M., de Castro, B. et al. Partition and location of nimesulide in EPC liposomes: a spectrophotometric and fluorescence study. Anal Bioanal Chem 377, 293–298 (2003). https://doi.org/10.1007/s00216-003-2089-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-003-2089-5

Keywords

Search

Navigation