Skip to main content
SpringerLink
Log in

Insertion and Partition of Sodium Taurocholate into Egg Phosphatidylcholine Vesicles

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose. To get a continuous description of the insertion and partition processes of sodium taurocholate (TC) into the lipid bilayers of vesicles that can serve as a model for understanding the mechanism of destabilization by the bile salts of liposomes used as drug carriers for oral administration.

Methods. The progressive solubilization of egg phosphatidylcholine vesicles during TC addition at controlled rates was followed by continuous turbidity (OD) and resonance energy transfer (RET) between two fluorescent probes. The influence of the lipid and TC concentrations as well as the rate of TC addition on the processes were examined.

Results. Continuous turbidity recordings allowed following of the size and composition evolutions of the mixed TC/lipid aggregates formed at different steps of the vesicle-micelle transition. The solubilization mechanism is governed by complex kinetics that depend on the surfactant concentration and its addition rate. A two-step process characterizes the evolution of the vesicular state: interaction of TC molecules with the external monolayer of the vesicles first occurs. The homogeneous distribution of TC within the lipid matrix after its insertion is a very slow process. A micellar structural reorganization is observed when TC is added rapidly.

Conclusions. This work provides detailed information on the slow insertion and diffusion kinetics of TC in liposomal bilayers by using a dynamic study which mimics physiological phenomena of digestion.

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

REFERENCES

  1. J. Dufourcq. Physico-chimie des phospholipides. In F. Puisieux (ed.), Les liposomes: applications thérapeutiques,Lavoisier, Paris, 1985, pp. 1-40.

    Google Scholar 

  2. M. Wacker and R. Schubert. From mixed micelles to liposomes: critical steps during detergent removal by membrane dialysis. Int. J. Pharm. 162:171–175 (1998).

    Google Scholar 

  3. D. J. Cabral and D. M. Small. Physical chemistry of bile. In S. G. Schultz, J. G. Forte and B. B. Rauner (eds.), Handbook of Physiology. The Gastrointestinal System , Section 6, Volume III, Oxford University Press, New York, 1989, pp. 621-662.

    Google Scholar 

  4. D. Lichtenberg. Liposomes as a model for solubilization and reconstitution of membranes. In Y. Barenholz and D.D. Lasic (eds.), Handbook of Nonmedical Applications of Liposomes, CRC Press, Boca Raton, 1996, pp. 199-218.

    Google Scholar 

  5. W. J. Xia and H. Onyuksel. Mechanistic studies on surfactantinduced membrane permeability enhancement. Pharm. Res. 17: 612–618 (2000).

    Google Scholar 

  6. J. Guo, Q. Ping, G. Sun, and C. Jiao. Lecithin vesicular carriers for transdermal delivery of cyclosporin A. Int. J. Pharm. 194:201–207 (2000).

    Google Scholar 

  7. M. Ollivon, S. Lesieur, C. Grabielle-Madelmont, and M. Paternostre. Vesicle reconstitution from lipid-detergent mixed micelles. Biochim. Biophys. Acta 1508:34–50 (2000).

    Google Scholar 

  8. N. A. Mazer. G.B Benedek, and M.C. Carey. Quasielastic light scattering studies of aqueous biliary lipid systems. Biochemistry 67:601–615 (1980).

    Google Scholar 

  9. P. Schurtenberger, N. Mazer, S. Waldvogel, and W. Känzig. Preparation of monodisperse vesicles with variable size by dilution of mixed micellar solutions of bile salts and phosphatidylcholine. Biochim. Biophys. Acta 775:111–114 (1984).

    Google Scholar 

  10. M.-T. Paternostre, M. Roux, and J. L. Rigaud. Mechanisms of membrane protein insertion into liposomes during reconstitution procedures involving the use of detergents. Biochemistry 27: 2668–2677 (1988).

    Google Scholar 

  11. A. S. Luk, E. W. Kaler, and S. P. Lee. Structural mechanisms of bile salt-induced growth of small unilamellar cholesterol-lecithin vesicles. Biochemistry 36:5633–5644 (1997).

    Google Scholar 

  12. A. Walter, P. K. Vinson, A. Kaplum, and Y. Talmon. Intermediate structures in the cholate-phosphatidylcholine vesiclemicelle transition. Biophys. J. 60:1315–1325 (1991).

    Google Scholar 

  13. S. Almog, T. Kushnir, S. Nir, and D. Lichtenberg. Kinetic and structured aspects of reconstitution of phosphatidylcholine vesicles by dilution of phosphatidylcholine-soduim cholate mixed micelles. Biochemistry 25:2597–2605 (1986).

    Google Scholar 

  14. R. Schubert, K. Beyer, H. Wolburg, and K. H. Schmidt. Structural changes in membranes of large unilamellar vesicles after binding of sodium cholate. Biochemistry 25:5263–5269 (1986).

    Google Scholar 

  15. K. Andrieux, L. Forte, G. Keller, C. Grabielle-Madelmont, S. Lesieur, M. Paternostre, C. Bourgaux, P. Lesieur, and M. Ollivon. Study of DPPC/TC/water phase diagram by coupling of synchrotron SAXS and DSC: I Equilibration kinetics. Progress Colloid Polymer Sci. 110:280–284 (1998).

    Google Scholar 

  16. L. Forte, K. Andrieux, G. Keller, C. Grabielle-Madelmont, S. Lesieur, M. Paternostre, C. Bourgaux, P. Lesieur, and M. Ollivon. Sodium taurocholate-induced lamellar-micellar phase transitions of DPPC determined by DSC and X-ray diffraction. J. Therm. Anal. 51:773–782 (1998).

    Google Scholar 

  17. C. H. Spink, V. Lieto, E. Mereand, and C. Pruden. Micelle-vesicle transition in phospholipid-bile-salt mixtures. A study by precision scanning calorimetry. Biochemistry 30:5104–5112 (1991).

    Google Scholar 

  18. S. U. Egelhaaf and P. Schurtenberger. Micelle-to-vesicle transition: a time-resolved structural study. Phys. Rev. Lett. 82:2804–2807 (1999).

    Google Scholar 

  19. J. Lasch. Interaction of detergents with lipid vesicles. Biochim. Biophys. Acta 1241:269–292 (1995).

    Google Scholar 

  20. M. Ollivon, O. Eidelman, R. Blumenthal, and A. Walter. Micellevesicle transition of egg phosphatidylcholine and octyl glucoside. Biochemistry 27:1695–1703 (1988).

    Google Scholar 

  21. G. A. Ramaldes, E. Fattal, F. Puisieux, and M. Ollivon. Solubilization kinetics of phospholipid vesicles by sodium taurocholate. Colloids and Surfaces B 6:363–371 (1996).

    Google Scholar 

  22. M.-T. Paternostre, O. Meyer, C. Grabielle-Madelmont, S. Lesieur, M. Ghanam, and M. Ollivon. Partition coefficient of a surfactant between aggretates and solution: Application to the micelle-vesicle transition of egg phosphatidylcholine and octyl β-Dglucopyranoside. Biophys. J. 69:2476–2488 (1995).

    Google Scholar 

  23. A. D. Bangham, M. M. Standish, and J. C. Watkins. Diffusion of univalent ions across the lamellae of swollen phospholipids. J. Mol. Biol. 13:238–252 (1965).

    Google Scholar 

  24. S. Lesieur, C. Grabielle-Madelmont, M.-T. Paternostre, and M. Ollivon. Size analysis and stability study of lipid vesicles by highperformance gel exclusion chromatography turbidity and dynamic light scattering. Anal. Biochem. 192:334–343 (1991).

    Google Scholar 

  25. F. J. Szoka, F. Olson, T. Heath, W. Vail, E. Mayhew, and D. Papahadjopoulos. Preparation of unilamellar liposomes of intermediaite size by a combination of reverse phase evaporation and through polycarbonate membranes. Biochim. Biophys. Acta 601: 559–571 (1980).

    Google Scholar 

  26. J. P. Kratohvil, W. P. Hsu, M. A. Jacobs, and T. M. Aminabhavi, and Y Mukunoki. Concentration-dependent aggregation patterns of conjugated bile salts in aqueous sodium chloride solutions. A comparison between sodium taurodeoxycholate and sodium taurocholate. Colloid Polymer Sci. 261:781–785 (1983).

    Google Scholar 

  27. K. Meguro, M. Ueno, and K. Esumi. Micelle formation in aqueous media. In M.J. Schick (ed.), Non Ionic Surfactants. Physical Chemistry,Marcel Dekker, New York, 1987, pp. 109-183.

    Google Scholar 

  28. S. Lesieur, C. Grabielle-Madelmont, M.-T. Paternostre, J. M. Moreau, R. M. Handjani-Vila, and M. Ollivon. Action of octylglucoside on non-ionic monoalkyl amphiphile-cholesterol vesicles study of solubilization mechanism. Chem. Phys. Lipids 56:109–121 (1990).

    Google Scholar 

  29. M. Ueno. Partition behavior of a nonionic detergent, octyl glucoside, between membranes and water phases and its effect on membrane permeability. Biochemistry 28:5631–5634 (1989).

    Google Scholar 

  30. K. Andrieux, S. Lesieur, M. Ollivon, and C. Grabielle-Madelmont. Methodology for vesicle permeability study by HPLC gel exclusion. J. Chromatogr. B 706:141–147 (1998).

    Google Scholar 

  31. K. Andrieux. Interactions des sels biliaires et des phospholipides: application à la transition vésicule-micelle, Ph. D. Thesis, Université Paris XI, 3 May 2000.

  32. C. Grabielle-Madelmont, A. Hochapfel, and M. Ollivon. Antibiotic-phospholipid interactions as studied by DSC and X-ray diffraction. J. Phys. Chem. 103:4534–4548 (1999).

    Google Scholar 

  33. P. Walde, J. Sumamoto, and C. J. O'Connor. The mechanism of liposomal damage by taurocholate. Biochim. Biophys. Acta 905: 30–38 (1987).

    Google Scholar 

  34. H. Saito, Y. Sugimoto, R. Tabeta, R. Suzuki, G. Izumi, M. Kodama, S. Toyoshima, and Ch. Nagata. Incorporation of bile acid of low concentration into model and biological membranes studied by 2H and 31P NMR. J. Biochem. (Tokyo) 94:1877–1887 (1983).

    Google Scholar 

  35. K. Müller. Structural dimorphism of bile salt/lecithin mixed micelles: a possible regulatory mechanism for cholesterol solubility in bile? X-ray structure analysis. Biochemistry 20:404–414 (1981).

    Google Scholar 

  36. M. A. Long, E. W. Kaler, and S. P. Lee. Stuctural characterization of the micelle-vesicle transition in lecithin-bile salt solutions. Biophys. J. 67:1733–1742 (1994).

    Google Scholar 

  37. C. Tanford. The Hydrophobic Effect: Formation of Micelles and Biological Membranes, Wiley, New York, 1973, chap. 10.

    Google Scholar 

  38. R. Schubert and K. H. Schmidt. Structural changes in vesicle membranes and mixed micelles of various lipid compositions after binding of different bile salts. Biochemistry 27:8787–8794 (1988).

    Google Scholar 

  39. G. A. Kossena, B. J. Boyd, C. J. Porter, and W. N. Charman. Separation and characterization of the colloidal phases produced on digestion of common formulation lipids and assessment of their impact on the apparent solubility of selected poorly watersoluble drugs. J. Pharm. Sci. 3:634–648 (2003).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Equipe Physicochimie des Systèmes Polyphasés, UMR CNRS 8612, 92296, Châtenay-Malabry cedex, France

    Karine Andrieux, Laura Forte, Sylviane Lesieur, Maité Paternostre, Michel Ollivon & Cécile Grabielle-Madelmont

Authors
  1. Karine Andrieux
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laura Forte
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sylviane Lesieur
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maité Paternostre
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michel Ollivon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cécile Grabielle-Madelmont
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Karine Andrieux.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Andrieux, K., Forte, L., Lesieur, S. et al. Insertion and Partition of Sodium Taurocholate into Egg Phosphatidylcholine Vesicles. Pharm Res 21, 1505–1516 (2004). https://doi.org/10.1023/B:PHAM.0000036927.37888.93

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:PHAM.0000036927.37888.93

Search

Navigation