Backofen, Michael and Schwach, Gregoire and Koechling, Wolfgang and Weiss, Torsten and Goepferich, Achim (2017) Polyanion based controlled release system for the GnRH-receptor antagonist degarelix. EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 104. pp. 65-71. ISSN 0928-0987, 1879-0720
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The aim of this study was to investigate the interaction between the positively charged gonadotropin releasing hormone receptor antagonist degarelix and the two polyanions alginate and carboxymethyl cellulose (CMC). Light as well as transmission electron microscopy revealed that complexes formed by simple mixing of the peptide with one of the polymers had a nano-structure consisting of twisted fibers. The remarkable unique process of complex formation could be followed by isothermal titration calorimetry: We found that peptide self aggregates dissolved upon the addition of polyanion and peptide-polymer-complexes formed thereafter with the anionic polymer as a template. Peptide release from the complexes was tested in vitro and in vivo and compared to the dissolution of drug from self-aggregates. In vitro the release was monitored over a period of three months. We could find only slight differences in the release kinetics for the alginate and the CMC complexes compared to the pure drug. An in vivo study in Sprague Dawley rats showed similar degarelix plasma concentration levels for the complex formulations and an aqueous degarelix solution following subcutaneous injection. Overall, our findings suggest a competition between complex formation and peptide aggregation, which did not increase the availability of free drug.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SUSTAINED-RELEASE; PROSTATE-CANCER; IN-VITRO; MICROPARTICLES; FORMULATION; PEPTIDES; PLGA; ACID; PH; GnRH antagonist; Sustained release; Polymer complex; ITC; TEM; In-vitro study |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:10 |
| Last Modified: | 15 Feb 2019 11:16 |
| URI: | https://pred.uni-regensburg.de/id/eprint/691 |
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