Abstract
The widespread use of enzymes as drugs or therapeutic agents has been limited by (a) enzyme availability, (b) biodegradation of administered enzyme, (c) immunogenecity of the enzyme as a foreign protein, and (d) accessibility of the enzyme to the appropriate site of action. It has become obvious that due to these limitations, the administration of free or native enzyme is not likely to be effective. Various mechanisms of protecting or packaging enzymes to offset some of these drawbacks have been described. We have been successful in producing conjugates of a number of different enzymes with a molar excess of homologous albumin. The resulting enzyme-albumin complex is resistant to proteolytic and heat inactivation and is apparently non-immunogenic. Using specific ligands crosslinked to the enzyme-albumin conjugate we have been able to target these conjugates to specific receptor sites and specific tissues. Ligands including cell surface-recognizing antibodies and hormones such as insulin have been used. These approaches offer new possibilities for the increased use of enzymes in medicine.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Purdon, H. S. (1871),Med. Times Gazette 1, 685.
Poznansky, M. J. (1983),Pharmacol. Therapeut. 21, 53.
Holcenberg, J. S., and Roberts, J. (1981),Enzymes as Drugs, Wiley, New York
Garrod, A. E. (1902),Lancet ii, 1616.
deDuve, C., and Watiaux, R. (1966),Annu. Rev. Physiol. 28, 435.
Hug, G. (1978),Pharm. Rev. 30, 565.
Brady, R. O., Barranger, J. A., Gal, A. E., Pentchev, P. G., Furbish, F. S., and Kusiak, J. W. (1981), inLysosomes and Lysosomal Storage Diseases, Callahan, J. W. and Lowden, J. A., eds., Raven Press, New York.
Brady, R. O., Barranger, J. A., Furbish, F. S., Stowens, D. W., and Ginns, E. I. (1982), inGaucher Disease: A Century of Delineation and Research, Desnick, R. J., Gatt S., and Grabowski, G. A., eds., Liss, New York.
Desnick, R. J., Thorpe, S. R., and Fiddler, M. B. (1976),Physiol. Rev. 56, 57.
Poznansky, M. J. and Cleland, L. G. (1980), inDrug Delivery Systems, Juliano, R., ed., Oxford, New York, pp. 253–315.
Furbish, F. S., Steer, C. J., Krett, N. L., and Barranger, J. A. (1981),Biochim. Biophys. Acta 673, 425.
Ehrlich, P. (1906), inCollected Studies on Immunity, Vol. 2, Wiley, New York, pp. 442–447.
Mathé, G., Trans Ba Loc, P., and Bernard, J. (1958),Compt. Rend. Acad. Sci. 246, 1626.
Gregoriadis, G. (1980), inLiposomes in Biological Systems, Gregoriadis, G., and Allison, A. C., eds., Wiley, New York, pp. 25–86.
Weereratne, H., Gregoriadis, G., Blair, H., and Purkiss, P. (1982), inAdvances in the Treatment of Inborn Errors of Metabolism, Crawfurd, M. d’A., Gibbs, D. A., and Watts, R. W. E., eds., Wiley, Chichester, pp. 143–160.
Chang, T. M. S., and Poznansky, M. J. (1968),Nature 218, 243.
Chang, T. M. S., Shu, C. D., Yu, Y. T., and Grunwald, J. (1982), inAdvances in the Treatment of Inborn Errors of Metabolism, Crawfurd, M. d’A., Gibbs, D. A., and Watts, R. W. E., eds., Wiley, Chichester, pp. 175–184.
Widder, K., Senyei, A. E., and Sears, B. (1982),J. Pharmaceut. Sci. 71, 379.
Humphreys, J. D., and Ihler, G. M. (1982), inOptimization of Drug Delivery, Alfred Benzon Symposium 17, Bundgaard, Hansen, and Kofad, eds., Munksgaard, Copenhagen, pp. 270–284.
Paillot, B., Remy, M. H., Thomas, D., and Broun, G. (1974).Pathol. Biol. 22, 491.
Remy, M. H., and Poznansky, M. J. (1978),Lancet ii, 68.
Poznansky, M. J. (1979),Life Sci. 24, 153.
Wong, K., Cleland, L. G., and Poznansky, M. J. (1980).Agents Actions 10, 231.
Poznansky, M. J., and Bhardwaj, D. (1980),Can. J. Physiol. Pharm. 58, 322.
Poznansky, M. J., and Bhardwaj, D. (1981),Biochem. J. 196, 89.
Poznansky, M. J., Shandling, M., Salkie, M. A., Elliott, J., and Lau, E. (1982),Cancer Res. 42, 1020.
Abuchowski, A., and Davis, F. F. (1981), inEnzymes as Drugs, J. S. Holcenburg and J. Roberts, eds., Wiley-Interscience, New York, pp. 367–384.
Seglen, P. O. (1973),Exp. Cell Res. 82, 391.
Flier, J. S., Kahn, R., and Roth, J. (1979),New Engl. J. Med. 300, 414.
Yagura, T., Kamisaki, Y., Wada, H., and Yamamura, Y. (1981),Int. Arch. Allergy Appl. Immunol. 64, 11.
Singh, B., Cliffe, B., and Poznansky, M. J. (1984), submitted for publication.
Bhardwaj, D., and Poznansky, M. J. (1984), submitted for publication.
Borel, Y. (1980),Immunol. Rev. 50, 71.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Poznansky, M.J. Enzyme—Albumin polymers. Appl Biochem Biotechnol 10, 41–56 (1984). https://doi.org/10.1007/BF02783734
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02783734