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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
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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

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