Abstract
Cetrorelix is a GnRH antagonist of the third generation. Its manifold therapeutic potential requires the adjustment of its resorption rates and effect profiles. The method of non-covalent complexation with suitable partner molecules enables the development of customized depot formulations. Investigating new partners and synthesis methods for Cetrorelix complexes we focused on maximal biocompatibility of the complexes. Compared to traditional depot forms the application of complexes aims at decreased aggregation of the peptide and increased biophily of the depots. The pharmacological properties of the new Cetrorelix complexes were analyzed by standardized dynamical in vitro liberation experiments. A new pharmacokinetic model has been developed and successfully applied for the quantitative analysis of the liberation profiles. With aromatic carboxylic acids and dipeptides we could synthesize stable complexes that have nearly linear release characteristics in aggregating environments close to in vivo conditions. The release rates were specific and very different for the complex partners. Thus several complexes have a great potential for a linear, characteristic release of the peptide in vivo and can be the basis for new depot forms for Cetrorelix.
Keywords: Cetrorelix, peptide hormone, complex, liberation, release, pharmacokinetics, aggregation
Current Drug Delivery
Title: Modification of the In Vitro Release Profile of Cetrorelix by Complexation with Biophilic Partners
Volume: 5 Issue: 4
Author(s): Thomas Rattei, Jurgen Engel, Wolfgang Naumann, Alexander Lang and Matthias Rischer
Affiliation:
Keywords: Cetrorelix, peptide hormone, complex, liberation, release, pharmacokinetics, aggregation
Abstract: Cetrorelix is a GnRH antagonist of the third generation. Its manifold therapeutic potential requires the adjustment of its resorption rates and effect profiles. The method of non-covalent complexation with suitable partner molecules enables the development of customized depot formulations. Investigating new partners and synthesis methods for Cetrorelix complexes we focused on maximal biocompatibility of the complexes. Compared to traditional depot forms the application of complexes aims at decreased aggregation of the peptide and increased biophily of the depots. The pharmacological properties of the new Cetrorelix complexes were analyzed by standardized dynamical in vitro liberation experiments. A new pharmacokinetic model has been developed and successfully applied for the quantitative analysis of the liberation profiles. With aromatic carboxylic acids and dipeptides we could synthesize stable complexes that have nearly linear release characteristics in aggregating environments close to in vivo conditions. The release rates were specific and very different for the complex partners. Thus several complexes have a great potential for a linear, characteristic release of the peptide in vivo and can be the basis for new depot forms for Cetrorelix.
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Cite this article as:
Rattei Thomas, Engel Jurgen, Naumann Wolfgang, Lang Alexander and Rischer Matthias, Modification of the In Vitro Release Profile of Cetrorelix by Complexation with Biophilic Partners, Current Drug Delivery 2008; 5 (4) . https://dx.doi.org/10.2174/156720108785915032
DOI https://dx.doi.org/10.2174/156720108785915032 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
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