Alternative Links zum Volltext:DOI
| Dokumentenart: | Artikel | ||||
|---|---|---|---|---|---|
| Titel eines Journals oder einer Zeitschrift: | Journal of Controlled Release | ||||
| Verlag: | Elsevier | ||||
| Band: | 172 | ||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 3 | ||||
| Seitenbereich: | S. 975-982 | ||||
| Datum: | 2013 | ||||
| Institutionen: | Chemie und Pharmazie > Institut für Pharmazie > Lehrstuhl Pharmazeutische Technologie (Prof. Göpferich) | ||||
| Identifikationsnummer: |
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| Stichwörter / Keywords: | Antibody; Biocompatibility; Bioavailability; Pharmacokinetics; Controlled release; Alginate | ||||
| Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 600 Technik 600 Technik, Medizin, angewandte Wissenschaften > 615 Pharmazie | ||||
| Status: | Veröffentlicht | ||||
| Begutachtet: | Ja, diese Version wurde begutachtet | ||||
| An der Universität Regensburg entstanden: | Zum Teil | ||||
| Dokumenten-ID: | 29287 |
Zusammenfassung
The sustained and localized delivery of monoclonal antibodies has become highly relevant, because of the increasing number of investigated local delivery applications in recent years. As the local delivery of antibodies is associated with high technological hurdles, very few successful approaches have been reported in the literature so far. Alginate-based delivery systems were previously ...
Zusammenfassung
The sustained and localized delivery of monoclonal antibodies has become highly relevant, because of the increasing number of investigated local delivery applications in recent years. As the local delivery of antibodies is associated with high technological hurdles, very few successful approaches have been reported in the literature so far. Alginate-based delivery systems were previously described as promising sustained release formulations for monoclonal antibodies (mAbs). In order to further investigate their applicability, a single-dose animal study was conducted to compare the biocompatibility, the pharmacokinetics and the bioavailability of a human monoclonal antibody liquid formulation with two alginate-based sustained delivery systems after subcutaneous administration in rats. 28 days after injection, the depot systems were still found in the subcutis of the animals. A calcium cross-linked alginate formulation, which was injected as a hydrogel, was present as multiple compartments separated by subcutaneous tissue. An in situ forming alginate formulation was recovered as a single compact and cohesive structure. It can be assumed that the multiple compartments of the hydrogel formulation led to almost identical pharmacokinetic profiles for all tested animals, whereas the compact nature of the in situ forming system resulted in large interindividual variations in pharmacokinetics. As compared to the liquid formulation the hydrogel formulations led to lower mAb serum levels, and the in situ forming system to a shift in the time to reach the maximum mAb serum concentration (Tmax) from 2 to 4 days. Importantly, it was shown that after 28 days only marginal amounts of residual mAb were present in the alginate matrix and in the tissue at the injection site indicating nearly complete release. In line with this finding, systemic drug bioavailability was not affected by using the controlled release systems. This study successfully demonstrates the suitability and underlines the potential of polyanionic systems for local and controlled mAb delivery.
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