Protein-Polyanion Interactions for the Controlled Release of Monoclonal Antibodies

Schweizer, Daniel and Schoenhammer, Karin and Jahn, Michael and Goepferich, Achim (2013) Protein-Polyanion Interactions for the Controlled Release of Monoclonal Antibodies. BIOMACROMOLECULES, 14 (1). pp. 75-83. ISSN 1525-7797, 1526-4602

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Abstract

The objective of the present study was to investigate ionic interactions between alginate and a monoclonal antibody (mAb1) and to utilize those interactions for the sustained release of mAb1. The existence of ionic interactions between alginate and mAb1 was strongly reflected by their rheological behavior. A 3-4 times increase in storage modulus (G') was observed by addition of 30 mg/mL mAb1 to a 20 mg/mL alginate solution. This increase was strongly dependent on pH and ionic strength. In vitro release studies revealed a marked pH-dependence of release rates and the reversibility of alginate-rnAb1 complexation under physiological conditions Two alginate-mAb1 sustained release formulations were developed by an internal gelation technique using CaCO3 and CaHPO4 as calcium sources for physical cross-linking. The CaCO3 formulation provided a stable pH-environment, optimally suited for pH-sensitive proteins. CaHPO4 led to a lower pH and stronger alginate-mAb1 interactions. The CaHPO4 cross-linked alginate released mAb1 over a period of 10-15 days. The long release period and changes in viscoelastic properties of alginate, when being mixed with mAb1, indicate the incorporation of mAb1 molecules into a mixed network with alginate. The results of this study demonstrate that ionic interactions between Polyanions and mAb1 are present and that they can be exploited for sustained release delivery of mAb1.

Item Type: Article
Uncontrolled Keywords: EMULSIFICATION INTERNAL GELATION; HUMAN-IMMUNOGLOBULIN-G; ALGINATE BEADS; IMMOBILIZATION MATERIAL; SUSTAINED-RELEASE; DELIVERY; STABILIZATION; FORMULATION; PHARMACOKINETICS; ENCAPSULATION;
Subjects: 600 Technology > 615 Pharmacy
Divisions: Chemistry and Pharmacy > Institute of Pharmacy
Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 29 Apr 2020 09:11
Last Modified: 29 Apr 2020 09:11
URI: https://pred.uni-regensburg.de/id/eprint/17504

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