TY - JOUR A1 - Wöhl-Bruhn, Stefanie A1 - Badar, Muhammad A1 - Bertz, Andreas A1 - Tiersch, Brigitte A1 - Koetz, Joachim A1 - Menzel, Henning A1 - Müller, Peter P. A1 - Bunjes, Heike T1 - Comparison of in vitro and in vivo protein release from hydrogel systems JF - Journal of controlled release N2 - 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 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. KW - In vivo imaging system (IVIS) KW - Hydrogel disks KW - Hydrogel microparticles KW - Release KW - In vivo-in vitro correlation KW - Hydroxyethyl starch (HES) Y1 - 2012 U6 - https://doi.org/10.1016/j.jconrel.2012.05.049 SN - 0168-3659 VL - 162 IS - 1 SP - 127 EP - 133 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Bertz, Andreas A1 - Wöhl-Bruhn, Stefanie A1 - Miethe, Sebastian A1 - Tiersch, Brigitte A1 - Koetz, Joachim A1 - Hust, Michael A1 - Bunjes, Heike A1 - Menzel, Henning T1 - Encapsulation of proteins in hydrogel carrier systems for controlled drug delivery influence of network structure and drug size on release rate JF - Journal of biotechnology N2 - Novel hydrogels based on hydroxyethyl starch modified with polyethylene glycol methacrylate (HES-P(EG)(6)MA) were developed as delivery system for the controlled release of proteins. Since the drug release behavior is supposed to be related to the pore structure of the hydrogel network the pore sizes were determined by cryo-SEM, which is a mild technique for imaging on a nanometer scale. The results showed a decreasing pore size and an increase in pore homogeneity with increasing polymer concentration. Furthermore, the mesh sizes of the hydrogels were calculated based on swelling data. Pore and mesh size were significantly different which indicates that both structures are present in the hydrogel. The resulting structural model was correlated with release data for bulk hydrogel cylinders loaded with FITC-dextran and hydrogel microspheres loaded with FITC-IgG and FITC-dextran of different molecular size. The initial release depended much on the relation between hydrodynamic diameter and pore size while the long term release of the incorporated substances was predominantly controlled by degradation of the network of the much smaller meshes. KW - Hydrogel KW - Hydrogel microspheres KW - Network structure KW - Release studies KW - Protein delivery KW - Mesh size Y1 - 2013 U6 - https://doi.org/10.1016/j.jbiotec.2012.06.036 SN - 0168-1656 VL - 163 IS - 2 SP - 243 EP - 249 PB - Elsevier CY - Amsterdam ER -