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J. Funct. Biomater. 2012, 3(4), 745-759; doi:10.3390/jfb3040745
Article

Hydration-Induced Phase Separation in Amphiphilic Polymer Matrices and its Influence on Voclosporin Release

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Received: 28 August 2012; in revised form: 11 October 2012 / Accepted: 18 October 2012 / Published: 30 October 2012
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Abstract: Voclosporin is a highly potent, new cyclosporine-A derivative that is currently in Phase 3 clinical trials in the USA as a potential treatment for inflammatory diseases of the eye. Voclosporin represents a number of very sparingly soluble drugs that are difficult to administer. We therefore selected it as a model drug that is dispersed within amphiphilic polymer matrices, and investigated the changing morphology of the matrices using neutron and x-ray scattering during voclosporin release and polymer resorption. The hydrophobic segments of the amphiphilic polymer chain are comprised of desaminotyrosyl-tyrosine ethyl ester (DTE) and desaminotyrosyl-tyrosine (DT), and the hydrophilic component is poly(ethylene glycol) (PEG). Water uptake in these matrices resulted in the phase separation of hydrophobic and hydrophilic domains that are a few hundred Angstroms apart. These water-driven morphological changes influenced the release profile of voclosporin and facilitated a burst-free release from the polymer. No such morphological reorganization was observed in poly(lactide-co-glycolide) (PLGA), which exhibits an extended lag period, followed by a burst-like release of voclosporin when the polymer was degraded. An understanding of the effect of polymer composition on the hydration behavior is central to understanding and controlling the phase behavior and resorption characteristics of the matrix for achieving long-term controlled release of hydrophobic drugs such as voclosporin.
Keywords: hydration-induced phase separation; amphiphilic polymer; resorption; voclosporin; small angle scattering hydration-induced phase separation; amphiphilic polymer; resorption; voclosporin; small angle scattering
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Khan, I.J.; Murthy, N.S.; Kohn, J. Hydration-Induced Phase Separation in Amphiphilic Polymer Matrices and its Influence on Voclosporin Release. J. Funct. Biomater. 2012, 3, 745-759.

AMA Style

Khan IJ, Murthy NS, Kohn J. Hydration-Induced Phase Separation in Amphiphilic Polymer Matrices and its Influence on Voclosporin Release. Journal of Functional Biomaterials. 2012; 3(4):745-759.

Chicago/Turabian Style

Khan, I. J.; Murthy, N. S.; Kohn, Joachim. 2012. "Hydration-Induced Phase Separation in Amphiphilic Polymer Matrices and its Influence on Voclosporin Release." J. Funct. Biomater. 3, no. 4: 745-759.


J. Funct. Biomater. EISSN 2079-4983 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert