Hostname: page-component-cd9895bd7-gvvz8 Total loading time: 0 Render date: 2024-12-27T02:15:16.586Z Has data issue: false hasContentIssue false
  • English
  • Français

Enzyme-Mediated Oscillatory Drug Release through Hydrogel Membranes

Published online by Cambridge University Press:  21 February 2011

John P. Baker  and
Ronald S. Siegel
John P. Baker
Affiliation:
School of Pharmacy S-926, University of California, San Francisco, CA 94143-0446
Ronald S. Siegel
Affiliation:
School of Pharmacy S-926, University of California, San Francisco, CA 94143-0446
Get access

Abstract

Implantable polymeric drug-delivery devices have been constructed to deliver drugs at welldefined rates. Typically, these devices have been designed to deliver drugs at a constant rate, or in response to the concentration of a certain body metabolite. For some drugs, pulsatile delivery is sought. For example, under normal conditions, human growth hormone is released in the body in periodic bursts. Current treatments for HGH deficiency often fail because HGH is not administered following the endogenous pattern. Thus, pulsatile hormone-replacement therapy should be considered. Also, it may be useful to deliver in a periodic, pulsatile manner drugs that exhibit significant acute tolerance.

Currently, an oscillator is under development that is fueled by endogenous compounds and contains a variable-permeability membrane. The membrane's permeability to the substrate of an enzymatic reaction is assumed to be dependent on the concentration of the product of the reaction in a manner that displays product inhibition. Under certain conditions, this negative-feedback control can lead to oscillations in the membrane's permeability to substrate. If the membrane's permeability to a drug is simultaneously affected, then this will lead to oscillatory drug release.

We report encouraging initial studies. A simple theoretical model has been developed for the membrane oscillator, and results of simulations based on the model are discussed.

Diffusion-cell studies have been performed with a variable-permeability poly(N-isopropylacrylamide- co-methacrylic acid) hydrogel membrane. Using glucose as a probe solute, the results show that lowering the pH induces hydrogel volume collapse and cessation of glucose permeation across the membrane.

Type
Research Article
Information
MRS Online Proceedings Library (OPL) , Volume 394: Symposium Z – Polymers in Medicine and Pharmacy , 1995 , 119
Copyright
Copyright © Materials Research Society 1995

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. Langer, R., Science 249, 1527 (1990).Google Scholar
2. Brabant, G., Prank, K. and Schofl, C., Trends in Endocrinology and Metabolism 3, 183 (1992).Google Scholar
3. Clark, R. G., Jansson, J. O., Isaksson, O. and Robinson, I., J. Endocrinol. 104, 53 (1985).Google Scholar
4. Katz, R. J., Cardiovasc. Drugs and Therapy 4, 247 (1990).Google Scholar
5. Dafters, R and Odber, J., Behav. Neurosci. 5, 1082 (1989).Google Scholar
6. Larter, R., Chem Rev. 90, 355 (1990).Google Scholar
7. Teorell, T., J. Gen. Physiol. 42, 831 (1959).Google Scholar
8. Caplan, S. R., Naparstek, A. and Zabusky, N. J., Nature 245, 364 (1973).Google Scholar
9. Naparstek, A., Thomas, D. and Caplan, S. R., Biochim. Biophys. Acta 323, 643 (1973).Google Scholar
10. Siegel, R. A. and Pitt, C. G., J. Controlled Release 33, 173 (1995).Google Scholar
11. Shen, P. D. and Larter, R., Biophys. J. 67, 1414 (1994).Google Scholar
12. Schild, H. G., Prog. Polym. Sci. 17, 163 (1992).Google Scholar
13. Dong, L.-C. and Hoffman, A. S., J. Controlled Release 13, 21 (1990).Google Scholar
14. Feil, H., Bae, Y.-H., Feijen, J. and Kim, S. W., Macromolecules 26, 2496 (1993).Google Scholar