Trends in Biotechnology
Volume 16, Issue 7, 1 July 1998, Pages 307-321
Journal home page for Trends in Biotechnology

Novel applications of liposomes

https://doi.org/10.1016/S0167-7799(98)01220-7Get rights and content

Abstract

Opinions of the usefulness of liposomes in various biotechnological applications range from unsubstantiated optimism to undeserved pessimism. This article reviews the background and development of liposomes, describes products that are commercially available and speculates optimistically about some future applications. The current deepening and widening of interest in liposomes in many scientific disciplines, and their application in medicine, immunology, diagnostics, cosmetics, ecology, cleansing and the food industry are promising novel breakthroughs and products.

Section snippets

Amphiphiles and self assembly

Molecules can be roughly divided into the polar and the nonpolar according to the symmetry and distribution of their electronic clouds. Polar molecules are soluble in polar solvents and insoluble in nonpolar solvents, and vice versa; for example, it is well known that oil and water do not mix. Some molecules, however, posses a polar and a nonpolar group on the same molecule; these molecules are called amphiphiles and, owing to hydrophilic and lipophilic interactions, they can self-organize and

Liposomes and sterically stabilized liposomes

Liposomes are microscopic spherical particles in which membranes, consisting of one or more lipid bilayers, encapsulate a fraction of the solvent in which they are suspended into their interior[1]. Studies during the 1970s and 1980s typically used ill-defined large multilamellar vesicles in the micrometre size range, while more recent investigations mostly use homogeneous unilamellar vesicles in the size range 50–150 nm. This size range is a compromise between loading efficiency of liposomes

Spontaneous formation of liposomes

Numerous papers claim erroneously that liposomes form spontaneously upon hydration of lipids. Without agitation, however, only few liposomes would form, caused by crystal defects and not to the spontaneity of liposome formation upon swelling of lipids. However, below, we shall show that this is exactly the feature that makes liposomes useful for drug encapsulation and delivery.

A few simple observations indicate that liposomes are not, in general, a thermodynamically stable state and so cannot

Industrial manufacture of liposomes

As for any new high-technology biotechnological discipline, the transfer from the academic bench to an industrial enterprise was crucial for liposomes. Although the first experiments in humans were performed with liposomes prepared fresh daily, any commercial product must have well-defined stability characteristics and a shelflife of over a year.

In contrast to the many pessimistic forecasts during the 1980s, the reproducible preparation of large volumes (in batches of hundreds of litres) of

Liposomes as drug-delivery vehicles

Liposomes resemble cell membranes in their structure and composition. They are typically made from natural, biodegradable, nontoxic and nonimmunogenic lipid molecules and can encapsulate or bind a variety of drug molecules into or onto their membranes. Consequently, all these properties make them attractive candidates for use as drug-delivery vehicles, as advocated by Schneider [his patent application for liposomes as drug-delivery systems in the mid-1960s was rejected because of a pre-existing

Medical applications of liposomes in humans

There are more than ten thousand papers on numerous medical applications of liposomes in various preclinical models. However, we shall concentrate only on liposome applications in humans.

In many cases, effective chemotherapy is severely limited by the toxic side effects of the drugs. Liposome encapsulation can alter the spatial and temporal distribution of the encapsulated drug molecules in the body, which may significantly reduce unwanted toxic side effects and increase the efficacy of the

Future prospects

Considering future medical applications of liposomes, we can expect several novel anticancer agents, cytokines, antifungals, antibiotics and antivirals in conventional and long-circulating liposomes. Their use may also spread into cardiovascular area, possibly by delivering prostaglandins, and the delivery of antisense oligonucleotides and ribozymes is also very promising. Novel modes of action may include: the development of liposomes as a long-circulating platform to bind and inactivate

Conclusion

The synergistic input from colloid science, physics, chemistry, biology, pharmacology and medicine has resulted in the successful development of liposomal drug delivery in less than 30 years, and the solid theoretical and experimental basis that have been developed promise new improvements and products1, 88, 98, 99, 100. Only time will tell which of the above applications and speculations will prove to be successful. However, based on the already available products, we can say that liposomes

References (108)

  • D Papahadjopoulos et al.

    Biochim. Biophys. Acta

    (1972)
  • M.J Parr et al.

    Biochim. Biophys. Acta

    (1994)
  • D Kirpotin et al.

    FEBS Lett.

    (1996)
  • A.M Klibanov et al.

    FEBS Lett.

    (1990)
  • J.H Senior et al.

    Biochim. Biophys. Acta

    (1991)
  • P.G de Gennes

    Adv. Polymer Sci.

    (1987)
  • T Kuhl et al.

    Biophys. J.

    (1994)
  • V.P Torchilin et al.

    Biochim. Biophys. Acta

    (1994)
  • S Zalipsky

    Adv. Drug Deliv. Rev.

    (1995)
  • T.M Allen

    Trends Pharm. Sci.

    (1994)
  • D.D Lasic

    J. Colloid Interface Sci.

    (1990)
  • G Haran et al.

    Biochim. Biophys. Acta

    (1993)
  • G Gregoriadis

    Trends Biotechnol.

    (1995)
  • T.M Allen et al.

    FEBS Lett.

    (1987)
  • R.K Jain

    Adv. Drug Deliv. Rev.

    (1997)
  • C.J Wheeler

    Biochim. Biophys. Acta

    (1996)
  • P Uster

    FEBS Lett.

    (1996)
  • R Gluck et al.

    Lancet

    (1994)
  • G Lee et al.

    Anal. Biochem.

    (1997)
  • Lasic, D. D. (1993) Liposomes: From Physics to Applications,...
  • Bangham, A. D., ed. (1983) Liposome Letters, Academic...
  • D.D Lasic et al.

    Science

    (1995)
  • Israelachvili, J. N. (1991) Intramolecular and Surface Forces, Academic...
  • M.B Yatvin et al.

    Science

    (1980)
  • J.R Silvius et al.

    Biochemistry

    (1993)
  • Lasic, D. D. (1997) Liposomes in Gene Delivery, CRC...
  • D Papahadjopoulos

    Proc. Natl. Acad. Sci. U. S. A.

    (1991)
  • M.C Woodle et al.

    Proceedings of the International Controlled Release Society

    (1990)
  • G Cevc et al.

    Biochim. Biophys. Acta

    (1990)
  • Lasic, D. D. and Martin, F. J., eds (1995) Stealth Liposomes, CRC...
  • D.D Lasic

    Angew. Chem., Int. Ed. Engl.

    (1994)
  • M Gouhan et al.

    Europhys. Lett.

    (1993)
  • D Needham et al.

    Biochim. Biophys. Acta

    (1991)
  • M.C Woodle et al.

    Bioconjugate Chem.

    (1994)
  • J.W Park

    Proc. Natl. Acad. Sci. U. S. A.

    (1995)
  • R.J Lee et al.

    J. Liposome Res.

    (1997)
  • D.B Kirpotin

    J. Liposome Res.

    (1997)
  • E Mayhew et al.

    Int. J. Cancer

    (1992)
  • J Vaage et al.

    Int. J. Cancer

    (1992)
  • F.C Franck

    Discuss. Faraday Soc.

    (1958)
  • W Helfrich

    Z. Naturforsch.

    (1973)
  • J.M Gebicki et al.

    Nature

    (1973)
  • J.W Hargreaves et al.

    Biochemistry

    (1978)
  • H Hauser

    Proc. Natl. Acad. Sci. U. S. A.

    (1984)
  • E.W Kaler et al.

    Science

    (1989)
  • R Joannic et al.

    Phys. Rev. Lett.

    (1997)
  • D.D Lasic

    Nature

    (1991)
  • Abeles, R. H., Frey, P. A. and Jencks, W. P. (1992) Biochemistry, Jones &...
  • Barenholz Y. and Crommelin, D. J. A. (1994) in Encyclopedia of Pharmaceutical Technology (Swarbick, L. and Boylan, J....
  • W Nichols et al.

    Biochim. Biophys. Acta

    (1976)
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