Skip to main content
SpringerLink
Log in

Liposomes as Carriers of Drugs Observations on Vesicle Fate after Injection and Its Control

  • Chapter
Artificial and Reconstituted Membrane Systems

Part of the book series: Subcellular Biochemistry ((SCBI,volume 14))

Abstract

Detailed knowledge of the behavior of liposomes (phospholipid vesicles) after injection is a prerequisite for their successful application as drug carriers in the therapy, prevention, or detection of disease (Gregoriadis, 1980). This discussion deals with two aspects: (1) the extent to which vesicles retain entrapped agents in the presence of biological fluids, namely, blood and (2) the rate by which vesicles are cleared from the circulation and their distribution in tissues. Evaluation of the first is likely to lead to methods of preventing or reducing agent leakage from the carrier en route to its target site. Study of the second aspect will contribute to the elucidation of the mechanism(s) through which vesicles leave the circulation to end up in tissues and also allow manipulations controlling vesicle clearance or uptake by tissues in need of pharmacological intervention. Both aspects have been discussed in detail elsewhere (Gregoriadis, 1983; Gregoriadis et al, 1983; Senior, 1987).

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abra, R. M., and Hunt, A., 1981, Liposome disposition in vivo: Dose and vesicle size effects. Biochim. Biophys. Acta 666:493–503.

    PubMed  CAS  Google Scholar 

  • Agarwal, K., Bali, A., and Gupta, C. M., 1986, Effect of phospholipid structure and survival times of liposomes in circulation. Biochim. Biophys. Acta 883:468–475.

    Article  PubMed  CAS  Google Scholar 

  • Allen, T. M., and Cleland, L. G., 1980, Serum-induced leakage of liposome contents. Biochim. Biophys. Acta 597:418–426.

    Article  PubMed  CAS  Google Scholar 

  • Allen, T. M., Ryan, J. L., and Papahadjopoulos, D., 1985, Gangliosides reduce leakage of aqueous-space markers from liposomes in the presence of human plasma. Biochim. Biophys. Acta 818:205–210.

    Article  PubMed  CAS  Google Scholar 

  • Barratt, G., Tenu, J. P., Yapo, A., and Petit, J.-F., 1986, Preparation and characterization of liposome containing mannosylated phospholipids capable of targeting drugs to macrophages. Biochim. Biophys. Acta 862:153–164.

    Article  PubMed  CAS  Google Scholar 

  • Damen, J., Regts, J., and Scherphof, G., 1981, Transfer and exchange of phospholipid between small unilamellar liposomes and rat plasma high density lipoproteins. Biochim. Biophys. Acta 665:538–545.

    PubMed  CAS  Google Scholar 

  • Dave, J., and Patel, H. M., 1986, Differentiation in hepatic and splenic phagocytic activity during reticuloendothelial blockade with cholesterol-free and cholesterol-rich liposomes. Biochim. Biophys. Acta 888:184–190.

    Article  PubMed  CAS  Google Scholar 

  • Garcon, N., Gregoriadis, G., Taylor, M., and Summerfield, J., 1988, Mannose-mediated targeted immunoadjuvant action of liposomes. Immunology 64:743–745.

    PubMed  CAS  Google Scholar 

  • Gregoriadis, G., 1973, Drug entrapment in liposomes. FEBS Lett. 36:292–296.

    Article  PubMed  CAS  Google Scholar 

  • Gregoriadis, G., 1980, Tailoring liposome structure. Nature (London) 283:814–815.

    Article  CAS  Google Scholar 

  • Gregoriadis, Gl, 1983, Targeting of drugs with molecules, cells and liposomes. Trends Pharmacol. Sci. 4:304–307.

    Article  CAS  Google Scholar 

  • Gregoriadis, G. (ed.), 1984, Liposome Technology, Vols. 1–3, CRC Press, Boca Raton, FL.

    Google Scholar 

  • Gregoriadis, G., 1985, Liposomes as carriers of drugs and vaccines. Trends Biotechnol. 3:235–241.

    Article  Google Scholar 

  • Gregoriadis, G. (ed.), 1988, Liposomes as Drug Carriers: Recent Trends and Progress, Wiley, Chichester.

    Google Scholar 

  • Gregoriadis, G., and Davis, C., 1979, Stability of liposomes in vivo and in vitro is promoted by their cholesterol content and the presence of blood cells. Biochim. Biophys. Res. Commun. 89:1287–1293.

    Article  CAS  Google Scholar 

  • Gregoriadis, G., and Neerunjun, D. E., 1974, Control of the rate of hepatic uptake and catabolism of liposome-entrapped proteins injected into rats. Possible therapeutic applications. Eur. J. Biochem. 47:179–185.

    Article  PubMed  CAS  Google Scholar 

  • Gregoriadis, G., and Ryman, B. E., 1972a, Fate of protein-containing liposomes injected into rats. An approach to the treatment of storage diseases. Eur. J. Biochem. 24:485–491.

    Article  PubMed  CAS  Google Scholar 

  • Gregoriadis, G., and Ryman, B. E., 1972b, Lysosomal localization of β-fructofuranosidase-containing liposomes injected into rats. Biochem. J. 129:123–133.

    PubMed  CAS  Google Scholar 

  • Gregoriadis, G., and Senior, J., 1980, The phospholipid component of small unilamellar liposomes controls the rate of clearance of entrapped solutes from the circulation. FEBS Lett. 119:43–46.

    Article  PubMed  CAS  Google Scholar 

  • Gregoriadis, G., and Senior, J., 1984, Targeting of small unilamellar liposomes to the galactose receptor in vivo. Biochem. Soc. Trans. 12:337–339.

    PubMed  CAS  Google Scholar 

  • Gregoriadis, G., Neerunjun, D., and Hunt, R., 1977, Fate of a liposome-associated agent injected into normal and tumour bearing rodents. Attempts to improve localization in tumour tissues. Life Sci. 21:357–370.

    Article  PubMed  CAS  Google Scholar 

  • Gregoriadis, G., Meehan, A., and Mah, M. M., 1981, Interaction of antibodies bearing small unilamellar liposomes with target free antigens in vitro and in vitro: Some influencing factors. Biochem. J. 200:203–210.

    PubMed  CAS  Google Scholar 

  • Gregoriadis, G., Kirby, C., and Senior, J., 1983, Optimization of liposome behaviour in vivo. Biol. Cell 47:11–18.

    CAS  Google Scholar 

  • Gregoriadis, G., Garcon, N., Senior J., and Davis, D., 1988, The immunoadjuvant action of liposomes: Nature of immune response and influence of liposomal characteristics, in Liposomes as Drug Carriers: Recent Trends and Progress (G. Gregoriadis, ed.), pp. 279–307, Wiley, Chichester.

    Google Scholar 

  • Guo, L. S. S., Hamilton, R. L., Goerke, J., Weinstein, J. N., and Havel, R. J., 1980, Interaction of unilamellar liposomes with serum lipoproteins and apoliproteins. J. Lipid Res. 21:993–1003.

    PubMed  CAS  Google Scholar 

  • Gupta, C. M., Bali, A., and Dhawan, S., 1981, Modification of phospholipid structure results in greater stability of liposomes in serum. Biochim. Biophys. Acta 648:192–198.

    Article  PubMed  CAS  Google Scholar 

  • Halks-Miller, M., Guo, L. S. S., and Hamilton, R. L., 1985, Tocopherol-phospholipid liposomes: Maximum content and stability to serum proteins. Lipids 20:195–200.

    Article  PubMed  CAS  Google Scholar 

  • Hwang, K. J., Luke, K. F. S., and Beaumier, P. L., 1980, Hepatic uptake and degradation of unilamellar sphingomyelin/cholesterol liposomes; A kinetic study. Proc. Natl. Acad. Sci. U.S.A. 77:4030–4034.

    Article  PubMed  CAS  Google Scholar 

  • Juliano, R. L., and Stamp, D., 1975, Effects of particle size and charge on the clearance of liposomes and liposome-encapsulated drugs. Biochem. Biophys. Res. Commun. 63:651–658.

    Article  PubMed  CAS  Google Scholar 

  • Kirby, C., and Gregoriadis, G., 1980, The effect of the cholesterol content of small unilamellar liposomes on the fate of their lipid components in vivo. Life Sci. 27:2223–2230.

    Article  PubMed  CAS  Google Scholar 

  • Kirby, C., and Gregoriadis, G., 1981, Plasma-induced release of solutes from small unilamellar liposomes is associated with pore formation in the bilayers. Biochem. J. 199:251–254.

    PubMed  CAS  Google Scholar 

  • Kirby, C., and Gregoriadis, G., 1983, The effect of lipid composition of small unilamellar liposomes containing melphalan and vincristine on drug clearance after injection into mice. Biochem. Pharmacol. 32:609–615.

    Article  PubMed  CAS  Google Scholar 

  • Kirby, C., Clarke, J., and Gregoriadis, G., 1980a, Effect of the cholesterol content of small unilamellar liposomes on their stability in vivo and in vitro. Biochem. J. 186:591–598.

    PubMed  CAS  Google Scholar 

  • Kirby, C., Clarke, J., and Gregoriadis, G., 1980b, Cholesterol content of small unilamellar liposomes controls phospholipid loss to high density lipoproteins in the presence of serum. FEBS Lett. 111:324–328.

    Article  PubMed  CAS  Google Scholar 

  • Krause, H. J., Juliano, R. L., and Regen, S., 1987, In viov behaviour of polymerized lipid vesicles. J. Pharm. Sci. 76:1–5.

    Article  PubMed  CAS  Google Scholar 

  • Krupp, L., Chobanian, A. V., and Brecher, J. P., 1977, The In viov transformation of phospholipid vesicles to a particle resembling HDL in the rat. Biochem. Biophys. Res. Commun. 722:1251–1258.

    Google Scholar 

  • Lelkes, P. I., and Tandeter, H. B., 1982, Studies on the methodology of the carboxyfluorescein assay and on the mechanism of liposome stabilization by red blood cells in vitro. Biochim. Biophys. Acta 716:410–419.

    Article  PubMed  CAS  Google Scholar 

  • Leserman, L. D., Machy, P., Deraux, C., and Barbet, J., 1983, Antibody-bearing liposomes: Targeting in vivo. Biol. Cell 47:111–116.

    Google Scholar 

  • Patel, H. M., Tuzel, N. S., and Ryman, B. E., 1983, Inhibitory effect of cholesterol on the uptake of liposomes by liver and spleen. Biochim. Biophys. Acta 761:142–151.

    Article  PubMed  CAS  Google Scholar 

  • Roerdink, F., Regts, J., Daemen, T., Bakker-Woudenberg, I., and Scherphof, G., 1986, Liposomes as drug carriers to liver macrophages: Fundamental and therapeutic aspects, in Targeting of Drugs with Synthetic Systems (G. Gregoriadis, J. Senior, and G. Poste, eds.), pp. 193–206 Plenum Press, New York.

    Google Scholar 

  • Ryman, B. E., and Tyrrell, D. A., 1980, Liposomes-Bags of potential, Essays Biochem. 16:49–98.

    PubMed  CAS  Google Scholar 

  • Scherphof, G., and Morselt, H., 1984, On the size-dependent disintegration of small unilamellar phosphatidylcholine vesicles in rat plasma. Biochem J. 221:423–429.

    PubMed  CAS  Google Scholar 

  • Scherphof, G., Roerdink, G., Waite, M., and Parks, J., 1978, Disintegration of phosphatidylcholine liposomes in plasma as a result of interaction with high-density lipoproteins. Biochim. Biophys. Acta 542:296–307.

    Article  PubMed  CAS  Google Scholar 

  • Segal, A. W., Willis, E. J., Richmond, J. E., Slavin, G., Black, C. D. V., and Gregoriadis, G., 1974, Morphological observations on the cellular and subcellular destination of intravenously administered liposomes. Br. J. Exp. Pathol. 55:320–327.

    PubMed  CAS  Google Scholar 

  • Senior, J., 1987, Fate and behaviour of liposomes in vivo: A review of controlling factors. CRC Crit. Rev. Therapeutic Drug Carrier Systems 3:123–193.

    CAS  Google Scholar 

  • Senior, J., and Gregoriadis, G., 1982a, Is half-life of circulating small unilamellar liposomes determined by changes in their permeability? FEBS Lett. 145:109–114.

    Article  PubMed  CAS  Google Scholar 

  • Senior, J., and Gregoriadis, G., 1982b, Stability of small unilamellar liposomes in serum and clearance from the circulation: The effect of the phospholipid and cholesterol components. Life Sci. 30:2123–2136.

    Article  PubMed  CAS  Google Scholar 

  • Senior, J., and Gregoriadis, G., 1984, Methodology in assessing liposomal stability in the presence of blood, clearance from the circulation of injected animals and uptake by tissues, in Liposome Technology (G. Gregoriadis, ed.), pp. 264–282, CRC Press, Boca Raton, FL.

    Google Scholar 

  • Senior, J., Gregoriadis, G., and Mitropoulos, K., 1983, Stability and clearance of small unilamellar liposomes: Studies with normal and lipoprotein-deficient mice. Biochim. Biophys. Acta 760:111–118.

    Article  PubMed  CAS  Google Scholar 

  • Senior, J., Crawley, J. C. W., and Gregoriadis, G., 1985, Tissue distribution of liposomes exhibiting long half-lives in the circulation after intravenous injection. Biochim. Biophys. Acta 839:1–8.

    Article  PubMed  CAS  Google Scholar 

  • Sila, M., Au, S., and Weiner, N., 1986, Effects of Triton X-100 concentration and incubation temperature on carboxyfluorescein release from multilamellar liposomes. Biochim. Biophys. Acta 859:165–170.

    Article  CAS  Google Scholar 

  • Spanjer, H. H., Van Berkel, T. J. C., Seherphof, G. L., and Kempen, H. J. M., 1985, The effect of a water-soluble tris-galactoside terminated cholesterol derivative on the In viov fate of small unilamellar vesicle in rats. Biochim. Biophys. Acta 816:396–402.

    Article  PubMed  CAS  Google Scholar 

  • Spanjer, H. H., Van Galen, M., Roerdink, F. H., Regts, J., and Seherphof, G., 1986, Intrahepatic distribution of small unilamellar liposomes as a function of liposomal lipid composition. Biochim. Biophys. Acta 863:224–230.

    Article  PubMed  CAS  Google Scholar 

  • Tall, A. R., 1980, Studies on the transfer of phosphatidylcholine from unilamellar vesicles into plasma high density lipoproteins in the rat. J. Lipid Res. 21:354–363.

    PubMed  CAS  Google Scholar 

  • Tall, A. R., and Small, D. M., 1977, Solubilisation of phospholipid membranes by human plasma high density lipoproteins. Nature (London) 265:163–164.

    Article  CAS  Google Scholar 

  • Tall, A. R., Forester, L. R., and Bongiovanni, G. L., 1983, Facilitation of phosphatidylcholine transfer into high density lipoproteins by an apoliprotein in the denisty of 1.20–1.26 gm/1 fraction of plasma. J. Lipid Res. 24:277–289.

    PubMed  CAS  Google Scholar 

  • Turner, A., Kirby, C., Senior, J., and Gregoriadis, G., 1983, Fate of cholesterol-rich unilamellar liposomes containing luIn-labelled bleomycin after subcutaneous injection into rats. Biochim. Biophys. Acta 760:119–125.

    Article  Google Scholar 

  • Weinstein, J. N., Blumenthal, R., Sharrow, S. O., and Henkart, P. A., 1978, Antibody-mediated targeting of liposomes: Binding to lymphocytes does not ensure incorporation of vesicle contents into the cells. Biochim. Biophys. Acta 509:272–288.

    Article  PubMed  CAS  Google Scholar 

  • Wolff, B., and Gregoriadis, G., 1984, The use of monoclonal anti-Thy1 IgG1 for the targeting of liposomes to AKR-A cells in vitro and in vivo. Biochim. Biophys. Acta 802:259–273.

    Article  PubMed  CAS  Google Scholar 

  • Yoshioka, S., Ishibashi, M., Shibazaki, T., and Uchiyama, M., 1984, Plasma induced instability of reverse-phase evaporation vesicles. J. Parenter. Sci. Technol. 38:222–227.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Research Council Group, Academic Department of Medicine, Royal Free Hospital School of Medicine, London, NW3 2QG, UK

    Gregory Gregoriadis

Authors
  1. Gregory Gregoriadis
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. North East Thames Regional Transfusion Centre, Brentwood, Essex, England

    J. R. Harris

  2. University of Paris VI, Paris, France

    A.-H. Etémadi

Rights and permissions

Reprints and permissions

Copyright information

© 1989 Plenum Press, New York

About this chapter

Cite this chapter

Gregoriadis, G. (1989). Liposomes as Carriers of Drugs Observations on Vesicle Fate after Injection and Its Control. In: Harris, J.R., Etémadi, AH. (eds) Artificial and Reconstituted Membrane Systems. Subcellular Biochemistry, vol 14. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-9362-7_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-9362-7_10

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-9364-1

  • Online ISBN: 978-1-4613-9362-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation