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Part of the book series: NATO ASI Series ((NSSA,volume 113))

Abstract

Liposomes that are developed to be used as drug carriers in therapy have to be sufficiently stable on storage. There is no consensus on the exact requirements, but shelf lives of over one year are certainly preferable. Liposomes can be unstable for a number of reasons. The liposome structure can change because of aggregation or fusion processes (physical stability), the associated drug can leak out of the vesicles and the phospholipids or the associated drug might be chemically unstable (hydrolysis, oxidation).1,2 All these changes might have an impact on the therapeutic effect of the product. Therefore, concepts were developed to improve liposome stability on storage. These concepts can be classified into three classes:

  1. 1)

    Storage of liposomes as aqueous dispersions.

  2. 2)

    Storage of liposomes in frozen condition or as a freeze dried product (removal of water by sublimation).

  3. 3)

    Storage of liposomes as concentrated dispersions or after removal of all “free” water via evaporation.

The “state of the art” and the pros and cons of these three approaches will be discussed in this contribution.

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References

  1. H.O. Hauser, 1971, The effect of ultrasonic irradiation on the chemical structure of egg lecithin, Biochem. Biophys. Res. Commun., 45:1049.

    Google Scholar 

  2. A.W.T. Konings, 1984, Lipid peroxidation in liposomes, in: Liposome Technology, G. Gregoriadis, ed., CRC Press, Inc., Boca Raton, Florida.

    Google Scholar 

  3. J.N. Weinstein, N. Yoshikami, P. Henkart, R. Blumenthal, and W.A. Hagins, 1977, Liposome-cell interaction. Transfer and intracellular release of a trapped fluorescent marker, Science, 195:489.

    Google Scholar 

  4. R. Goldman, T. Facchinetti, D. Bach, A. Raz, and M. Shinitzky, 1978, A differential interaction of daunomycin, adriamycin and their derivatives with human erythrocytes and phospholipid bilayers, Biochim, Biophys. Acta, 512:254.

    Google Scholar 

  5. E. Goormaghtigh, P. Chatelain, J. Caspers, and J.M. Ruysschaert, 1980, Evidence of a specific complex between adriamycin and negatively charged phospholipids, Biochim. Biophys. Acta, 597:1.

    Google Scholar 

  6. J. Wilschut, 1982, Preparation and properties of phosphilipid vesicles, in: Methodologie des Liposomes, L.D. Leserman and J. Barbet, eds., Editions INSERM, Vol. 107, Paris.

    Google Scholar 

  7. F. Olson, C.A. Hunt, P. Szoka, W.J. Vail, and D. Papahadjopoulos, 1979, Preparation of liposomes of defined size distribution by extrusion through polycarbonate membranes, Biochim. Biophys. Acta, 557:9.

    Google Scholar 

  8. E.M.G. Van Bommel and D.J.A. Crommelin, 1984, Stability of doxorubicin-liposomes on storage: as an aqueous dispersion, frozen or freeze dried, Int. J. Pharm., 22:299.

    Google Scholar 

  9. S. Frokjaer, E.L. Hjorth, and O. Worts, 1982, Stability and storage of liposomes, in: Optimization of Drug Delivery, H. Bundgaard, A. Bagger-Hansen, and H. Kofod, eds., Munkgaard, Copenhagen.

    Google Scholar 

  10. C.A. Hunt and S. Tsang, 1981, Alpha-Tocopherol retards autoxidation and prolongs the shelf-life of liposomes, Int. J. Pharm., 8:101.

    Google Scholar 

  11. M.J.H. Janssen, D.J.A. Crommelin, G. Storm, and A. Hulshoff, 1985, Doxorubicin decomposition on storage. Effects of the pH, buffer components and liposome encapsulation, Int. J. Pharm., 23:1.

    Google Scholar 

  12. J.R. Evans, F.J.Th. Fildes, and J.E. Oliver, 1978, Liposome, Deutsches Patentant 2818655.

    Google Scholar 

  13. G. Vanderberghe and R. Handjani, 1979, Improving the storage stability of aqueous dispersions of spherules, U.K. Patent Application GB 2013609 A.

    Google Scholar 

  14. R.E. Gordon, P.R. Mayer, and D.O. Kildsig, 1982, Lyophilization as a means of increasing shelf-life of phospholipid bilayer vesicles, Drug Devel. and Ind. Pharm., 8:465.

    Google Scholar 

  15. S. Henry-Michelland, P. Poly, P. Puisieux, J. Delattre, and J. Likforman, 1983, Etude du compottement des liposomes lors d’experiments de congelation-decongelation et de lyophilisation: influence des cryo-protecteurs, CR. 3eme Congres International de Technologie Pharmaceutique, APGI ed., Paris.

    Google Scholar 

  16. J.H. Crowe, L.M. Crowe, and R. Mouradian, 1983, Stabilization of

    Google Scholar 

  17. biological membranes at low water activities, Cryobiology, 20:346.

    Google Scholar 

  18. D.J.A. Crommelin and E.M.G. Van Bommel, 1984, Stability of liposomes on storage: freeze dried, frozen or as an aqueous dispersion, Pharm. Res., 1:159.

    Google Scholar 

  19. S.S. Abu-Zaid, M. Moril, and N. Takeguchi, 1984, Effects of freezing, freeze drying and cold storage on the size and membrane permeability of multilamellar liposomes, Membrane 9:43.

    Article  CAS  Google Scholar 

  20. P.M. Shulkin, S.E. Seltzer, M.A. Davis, and D.F. Adams, 1984, Lyophilized liposomes: a new method for long term vesicular storage, J. Microencap., 1:73.

    Article  CAS  Google Scholar 

  21. G. Storm, L. Van Bloois, M. Brouwer, and D.J.A. Crommelin, The interaction of cytostatic drugs with adsorbents in aqueous media. The potential implications for liposome preparation, Biochim. Biophys. Acta, 818:343.

    Google Scholar 

  22. G.J. Fransen, P.J.M. Salemink, and D.J.A. Crommelin, 1986, Critical parameters in freezing of liposomes, Biochim, Biophys. Acta, submitted for publication.

    Google Scholar 

  23. P. Mazur, 1970, Cryobiology: the freezing of biological systems, Science, 168:939.

    Article  CAS  Google Scholar 

  24. M.J. Ashwood-Smith, and J. Farrant, eds., 1980, Low Temperature Preservation in Medicine and Biology, Pitman Medical Ltd., Tunnbridge Wells, Kent.

    Google Scholar 

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© 1986 Plenum Press, New York

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Crommelin, D.J.A., Fransen, G.J., Salemink, P.J.M. (1986). Stability of Liposomes on Storage. In: Gregoriadis, G., Senior, J., Poste, G. (eds) Targeting of Drugs With Synthetic Systems. NATO ASI Series, vol 113. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5185-6_20

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  • DOI: https://doi.org/10.1007/978-1-4684-5185-6_20

  • Publisher Name: Springer, Boston, MA

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