Hostname: page-component-586b7cd67f-rcrh6 Total loading time: 0 Render date: 2024-11-25T17:28:06.250Z Has data issue: false hasContentIssue false
  • English
  • Français

Sustained Delivery of Bioactive Polypeptide by Compression in Lipid Admixture

Published online by Cambridge University Press:  26 February 2011

Paul Y. Wang
Paul Y. Wang*
Affiliation:
Laboratory of Chemical Biology, Institute of Biomedical Engineering, Faculty of Medicine, University of Toronto, Toronto, Canada M5S 1A8
Get access

Abstract

Bioactive polypeptides are susceptible to inactivation by proteolytic enzymes in body fluids. Instead of many injections, these polypeptides may be specially formulated to prolong their action in vivo to several months by entrapment in a polymer mixture. In a recent fundamental study on implant for drug delivery, it was found in this laboratory that a polymer support component was not mandatory and pharmacologically active macromolecules could be readily delivered on a sustained basis. Consequently, when 10% insulin (Zn) was admixed with cholesterol and then compressed, the hormone action was extended to about 20 days when tested subcutaneously in Wistar rats with streptozotocin-induced diabetes. Evaluation of other lipids has shown that with palmitic acid as the excipient, the 8-hr action of insulin can be extended to about 40 days. The same type of sustained delivery implant containing insulin or pituitary growth hormone can enhance growth in normal Wistar rats. Since no synthetic materials were used, biocompatibility problem is not expected. Further, the fatty acid excipient is gradually eroded in vivo, and explantation of the implant will not be necessary as well. This approach shall be particularly useful in special formulations of other pharmaceutical proteins such as the rDNA-produced somatotropin analog used in growth enhancement of farm animals raised for consumer food products.

Type
Research Article
Information
MRS Online Proceedings Library (OPL) , Volume 110: Symposium M – Biomedical Materials and Devices , 1987 , 407
Copyright
Copyright © Materials Research Society 1988

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Mathiowitz, E., Leong, K., and Langer, R., Proc. 12th International Symposium Controlled Release Bioactive Materials (Controlled Release Society, Lincolnshire, IL, 1985) pp. 183–184.Google Scholar
2. Brown, L., Munoz, C., Siemer, L., Edelman, E., and Langer, R., Diabetes 35, 692 (1986).Google Scholar
3. Eppard, P.J., Bauman, D.E., and McCutcheon, S.N., J. Dairy Sci. 68, 1109 (1985).Google Scholar
4. Marx, W., Simpson, M.E., and Evans, H.M., Endocrinology 30, 1 (1942).CrossRefGoogle Scholar
5. Wang, P.Y., Diabetes 36, 1068 (1987).Google Scholar
6. Greenspan, F.S., Li, C.H., Simpson, M.E., and Evans, H.M., Endocrinology 45, 455 (1949).CrossRefGoogle Scholar
7. Groesbeck, M.D., Parlow, A.F., and Daughaday, W.H., Endocrinology 120, 1963 (1987).CrossRefGoogle Scholar
8. Pickup, J.C. and Stevenson, R.W. in Rate-Controlled Drug Administration and Action, edited by Struyker-Boudier, H.A.J. (CRC Press, Boca Raton, FL 1986) pp. 143–170.Google Scholar
9. Goosen, M.F.A., Leung, Y.F., O'Shea, G.M., Chou, S., and Sun, A.M., Diabetes 32, 478 (1983).Google Scholar
10. Wang, P.Y. (unpublished).Google Scholar