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Comparison of in vitro and in vivo protein release from hydrogel systems

  • Hydrogel systems based on hydroxyethyl starch-polyethylene glycol methacrylate (HES-P(EG)(6)MA) or hydroxyethyl starch methacrylate (HES-MA) were used to assess the protein release behavior. Here, we analyzed the in vitro release of FITC-anti-human antibodies incorporated in either HES-P(EG)(6)MA or HES-MA hydrogel delivery systems in PBS or human serum. In addition, hydrogel disks and microparticles prepared from the two polymers were subcutaneously implanted in BALB/c mice. The in vivo release of FITC-IgG was non-invasively monitored by an in vivo imaging system (IVIS 200) over a time period of up to 3 months. The imaging system allowed to asses individual animals over time, therefore only a small number of animals was required to obtain high quality data. The reduction in fluorescence intensity at the site of administration was compared to in vitro release profiles. These investigations demonstrated a sustained release from HES-MA hydrogel disks compared to rapidly degrading HES-P(EG)(6)MA disks and microparticles. The sustainedHydrogel systems based on hydroxyethyl starch-polyethylene glycol methacrylate (HES-P(EG)(6)MA) or hydroxyethyl starch methacrylate (HES-MA) were used to assess the protein release behavior. Here, we analyzed the in vitro release of FITC-anti-human antibodies incorporated in either HES-P(EG)(6)MA or HES-MA hydrogel delivery systems in PBS or human serum. In addition, hydrogel disks and microparticles prepared from the two polymers were subcutaneously implanted in BALB/c mice. The in vivo release of FITC-IgG was non-invasively monitored by an in vivo imaging system (IVIS 200) over a time period of up to 3 months. The imaging system allowed to asses individual animals over time, therefore only a small number of animals was required to obtain high quality data. The reduction in fluorescence intensity at the site of administration was compared to in vitro release profiles. These investigations demonstrated a sustained release from HES-MA hydrogel disks compared to rapidly degrading HES-P(EG)(6)MA disks and microparticles. The sustained release from HES-MA disks could be further optimized by using increased polymer concentrations. Human serum as in vitro release medium reflected better the in vivo release from HES-P(EG)(6)MA systems than PBS, suggesting that the presence of organic substances like proteins or lipids may play a significant role for the release kinetics.show moreshow less

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Author details:Stefanie Wöhl-Bruhn, Muhammad Badar, Andreas Bertz, Brigitte TierschORCiD, Joachim KoetzORCiDGND, Henning Menzel, Peter P. Müller, Heike Bunjes
DOI:https://doi.org/10.1016/j.jconrel.2012.05.049
ISSN:0168-3659
Title of parent work (English):Journal of controlled release
Publisher:Elsevier
Place of publishing:Amsterdam
Publication type:Article
Language:English
Year of first publication:2012
Publication year:2012
Release date:2017/03/26
Tag:Hydrogel disks; Hydrogel microparticles; Hydroxyethyl starch (HES); In vivo imaging system (IVIS); In vivo-in vitro correlation; Release
Volume:162
Issue:1
Number of pages:7
First page:127
Last Page:133
Funding institution:German Research Foundation (DFG) [SFB 578]; DAAD-HEC fellowship program; collaboration research center [SFB 599]
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Chemie
Peer review:Referiert
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