Hostname: page-component-76fb5796d-vvkck Total loading time: 0 Render date: 2024-04-26T03:21:36.597Z Has data issue: false hasContentIssue false

Design of pH Sensitive Materials for On/Off Release of Thrombolytic and Anticoagulant Drugs

Published online by Cambridge University Press:  15 March 2011

Angela M. Thornton
Affiliation:
The University of Alabama, Department of Chemical Engineering Tuscaloosa, AL 35487, U.S.A
Christopher S. Brazel
Affiliation:
The University of Alabama, Department of Chemical Engineering Tuscaloosa, AL 35487, U.S.A
Get access

Abstract

An experimental study was conducted to determine the mechanisms of transport for delivery of cardiovascular agents using a pH-sensitive hydrogel as the carrier. Copolymer gels based on hydrophilic (2-hydroxyethyl methacrylate) and polybasic (N,N-diethylaminoethyl methacrylate) monomers were formed as membranes and analyzed for their potential to control the diffusion of model solutes as well as heparin and streptokinase. The polybasic materials were selected because they would allow drug delivery to be triggered by microenvironmental pH fluctuations around the site of a blood clot. In slightly basic solutions, the polymers remained in a thermodynamic state of phase-separation, while the polymer absorbed more solution and the mesh size increased once the pH was less than the pKb of the polybasic moiety. The hydrogels' equilibrium swelling ratios were determined as a function of pH, and the mesh sizes were determined by rubber elasticity measurements. Diffusion of model solutes, as well as heparin, was studied using side-by-side diffusion cells to determine the influence of gel morphology and mesh size on the screening of the solutes. Streptokinase release from these gels was modulated by environmental pH.

Type
Research Article
Copyright
Copyright © Materials Research Society 2001

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. Byun, Y. and Yang, V.C, ASAIO Journal, 1998, M638.Google Scholar
2. Torchilin, V.P., Advanced Drug Delivery Rev., 17, 75 (1995).Google Scholar
3. Brazel, C.S. and Peppas, N.A. in Biomaterials for Drug and Cell Delivery, edited by Murphy, R.M., Mikos, A.G., Bernstein, H. and Peppas, N.A., (Mater. Res. Soc. Proc. 331, Pittsburgh, PA, 1994) pp. 211216.Google Scholar
4. Vakkalanka, S.K., S.K., , Brazel, C.S. and Peppas, N.A., J. Biomater. Sci., Polym. Ed., 8, 119 (1996).Google Scholar
5. Gutowska, A., Bae, Y.H., Feijen, J., and Kim, S.W., J. Control. Rel., 22, 250 (1992).Google Scholar
6. Gutowska, A., Bae, Y.H., Jacobs, H., Mohammad, F., Mix, D., Feijen, J., and Kim, S.W., J. Biomed. Mater. Res., 29, 811 (1995).Google Scholar
7. Brazel, C.S. and Peppas, N.A., J. Control. Rel., 39 57 (1996).Google Scholar
8. Lewis, A.E., Principles of Hematology, (Appleton-Century-Crofts, New York, 1970), p. 3637.Google Scholar
9. Ende, M.T. am, Hariharan, D. and Peppas, N.A., Reactive Polymers, 25, 127 (1995).Google Scholar
10. Peppas, N.A. and Moynihan, H.J., in Hydrogels in Medicine and Pharmacy, Volume II, edited by Peppas, N.A. (CRC Press, Boca Raton, FL, 1987), pp. 4964.Google Scholar
11. Hariharan, D., Peppas, N.A., Polymer, 37, 1, 149 (1996).Google Scholar
12. Cornejo-Bravo, J.M., Arias-Sanchez, V., Alvarez-Anguiano, A. and Siegel, R.A., J. Control. Rel., 33, 223 (1995).Google Scholar
13. Lowman, A. M. and Peppas, N.A., Macromolecules, 30, 4959 (1997).Google Scholar
14. MacIntosh, F.C., Biochemistry, 35, 776 (1941).Google Scholar