Drug Delivery via Cell-Surface Receptors

  • T. Y. Shen
Part of the Experimental Biology and Medicine book series (EBAM, volume 7)

Abstract

Cell-surface receptors are noted for their high degree of specificity in their interactions with appropriate ligands. In receptor mediated drug delivery the drug is attached to or associated with a ligand which recognizes a specific receptor on the surface of a target cell. The ligand can be a component of a phospholipid vesicle, e.g. liposome, a lipoprotein particle or a chemical derivative of a macromolecule, small peptide or oligosaccharide (Fig. 1). After ingestion the active free drug is liberated by intracellular enzymes to exert its pharmacological effect.

Keywords

Cholesterol Carbohydrate Polysaccharide Lysine Dexamethasone 

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References

  1. Doebber, T.W., Wu, M.S., Bugianesi, R.L., Ponpipom, M.M., Furbish, F.S., Barranger, J.A., Brady, R.O. and Shen, T.Y., Enhanced macrophage uptake of synthetically glycosylated human placental β-glucocerebrosidase. J. Biol. Chem., 257, (1982) 2193–2199.PubMedGoogle Scholar
  2. Firestone, R.A., Pisano, J.M., Falck, J.R., McPhaul, M.M. & Krieger, M., Delivery of cyto-toxic compounds to cells by the LDL pathway. J Med. Chem., 27 (1984) 1037–1043.PubMedCrossRefGoogle Scholar
  3. Ghosh, P., Das, P.K., and Bachhawat, G.K., Targeting of liposomes towards different cell types of rat liver through the involvement of liposomal surface glycosides. Arch. of Biochem. and Biophysics, 213 (1982) 266–270.CrossRefGoogle Scholar
  4. Goldstein, J.L. and Brown, H.S., The low density lipoprotein pathway and its relation to atherosclerosis. Annu. Rev. Biochem., 46 (1977) 897–930.CrossRefGoogle Scholar
  5. Iwamoto, K., Sunamoto, J., Inoue, K., Endo, T. and Nojima, S., Importance of surface structure in liposomal membranes of glyceroglycolipids. Biochimica et Biophysica Acta, 691 (1982) 44–51.CrossRefGoogle Scholar
  6. Krieger, M., Goldstein, J.L. & Brown, M.S., Receptor-mediated uptake of low-density lipoprotein reconsitituted with 25-hydroxycholesteryl oleate suppresses 3-hydroxy-3-methylglutaryl-coenzyme-a reductase and inhibits growth of human fibroblasts. Proc. Natl. Acad. Sci. USA, 75 (1978) 5052–5056.PubMedCrossRefGoogle Scholar
  7. Krieger, M., Brown, H.S., Faust, J.R. & Goldstein, J.L., Replacement of endogenous cholesteryl esters of low densitylipoprotein with exogenous cholesteryl linoleate–reconsitution of a biologically active lipoprotein particle. J. Bio. Chem., 253 (1978) 4093–4101.Google Scholar
  8. Latif, N. & Bachhawat, B.K., The effect of surface sugars on liposomes in immunopotentiation. Immuno. Letters, 8 (1984) 75–78.CrossRefGoogle Scholar
  9. Lee, R.T., Lin, P., and Lee, Y.C., New synthetic cluster ligands for galactose/N-acetylgalactosamine specific lectin of Mammalian liver. Biochem., 23, (1984) 4255–4261.CrossRefGoogle Scholar
  10. Mahley, R.W. and Innerarity, T.L., Lipoprotein receptors and cholesterol homeostasis. Biochimica et Biophysica, Acta., 737 (1983) 197–222.Google Scholar
  11. Mosley, S.T., Goldstein, J.L., Brown, M.S., Falck, J.R. & Anderson, R.G., Targeted killing of cultured cells by receptor dependent photosensitization. Proc. Natl. Acad. Sci. USA, 78 (1981) 5717–5721.PubMedCrossRefGoogle Scholar
  12. Murray, G.J., Doebber, T.W., Wu, M.S., Bugianesi, R.L., Ponpipom, M.M., Shen, T.Y., Brady, R.O., & Barranger, J.A., Targeting of synthetically glycosylated human placental glucocerebrosidase. (in press)Google Scholar
  13. Nicolau, C., Legrand, A., & Soriano, P., Liposomes for gene transfer and expression in vivo. Ctr. Biophys. Molec., CNRS, Ciba Foundation Symposia, No. 103, (1984) 254–264.Google Scholar
  14. Pompipom, M.H., Bugianesi, R.L., and Shen, T.Y., Cell surface carbohydrates for targeting studies. Canadian J of Chem., 58, (1980) 214–220.CrossRefGoogle Scholar
  15. Robbins, J.C., Lam, M.H., Tripp, C.S., Bugianesi, R.L., Ponpipom, H.M. and Shen, T.Y., Synthetic glycopeptide substrates for receptor mediated endocytosis by macrophages. Proc. Natl. Acad. Sci. USA, 78 (1981) 7294–7298.PubMedCrossRefGoogle Scholar
  16. Soriano, P., Dijkstra, J., Legrand, A., Spanjer, H., Londos-Gagliardi, D., Roerdink, F., Scherphos, G. and Nicolau, C., Targeted and nontargeted liposomes for in vivo transfer to rat liver cells of plasmid containing the preproinsulin I gene. Proc. Natl. Acad. Sci. USA, 80 (1983) 7128–7131PubMedCrossRefGoogle Scholar
  17. Wu, P.S., Wu, H.M., Tin, G.W., Schuh, J.R., Croasmun, W.R., Baldeschwieler, J.D., Shen, T.Y., and Ponpipom, H.M., Stability of carbohydrate modified vesicles in vivo: Comparative effects of ceramide and cholesterol glycoconjugates. Proc. Natl. Acad. Sci. USA, 79, (1982) 5490–5493.PubMedCrossRefGoogle Scholar

Copyright information

© The Humana Press Inc. 1985

Authors and Affiliations

  • T. Y. Shen
    • 1
  1. 1.Merck Sharp & Dohme Research LaboratoriesRahwayUSA

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