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Pharmacokinetics, biocompatibility and bioavailability of a controlled release monoclonal antibody formulation

Schweizer, D, Vostiar, I, Heier, A, Serno, T, Schoenhammer, K, Jahn, M, Jones, S, Piequet, A, Beerli, C, Gram, H and Goepferich, A (2013) Pharmacokinetics, biocompatibility and bioavailability of a controlled release monoclonal antibody formulation. JOURNAL OF CONTROLLED RELEASE. pp. 975-982.


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 (T-max) 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. (C) 2013 Elsevier B.V. All rights reserved

Item Type: Article
Additional Information: pubid: 168 nvp_institute: NIBR contributor_address: Novartis Pharma AG, Biol Proc Res & Dev, CH-4002 Basel, Switzerland ; Novartis Pharma AG, Novartis Inst BioMed Res, CH-4002 Basel, Switzerland ; Univ Regensburg, Dept Pharmaceut Technol, D-93053 Regensburg, Germany; Novartis Pharma AG, Biol Proc Res & Dev, CH-4002 Basel, Switzerland; Goepferich, A; Univ Regensburg, Dept Pharmaceut Technol, Univ Str 31, D-93053 Regensburg, Germany
Date Deposited: 13 Oct 2015 13:12
Last Modified: 13 Oct 2015 13:12