Diels-Alder Hydrogels for Controlled Antibody Release: Correlation between Mesh Size and Release Rate.
Eight-armed PEG, molecular mass 10 kDa, was functionalized with furyl and maleimide groups, respectively; the obtained macromonomers were cross-linked via Diels-Alder chemistry. The mesh size (ξ) of the prepared hydrogels was determined by swelling studies, rheology, and low field NMR spectroscopy. The in vitro release of fluorescein isothiocyanate labeled dextrans (FDs) and bevacizumab was investigated. The average mesh size (ξavg) increased from 5.8 ± 0.1 nm to 56 ± 13 nm during degradation, as determined by swelling studies. The result of the rheological measurements (8.0 nm) matched the initial value of ξavg. Low field NMR spectroscopy enabled the determination of the mesh size distribution; the most abundant mesh size was found to be 9.2 nm. In combination with the hydrodynamic radius of the molecule (Rh), the time-dependent increase of ξavg was used to predict the release profiles of incorporated FDs applying an obstruction-scaling model. The predicted release profiles matched the experimentally determined release profiles when Rh < ξavg. However, significant deviations from the theoretical predictions were observed when Rh ≥ ξavg, most likely due to the statistical distribution of ξ in real polymer networks. The release profile of bevacizumab differed from those of equivalently sized FDs. The delayed release of bevacizumab was most likely a result of the globular structure and rigidity of the protein. The observed correlation between ξ and the release rate could facilitate the design of controlled release systems for antibodies.
Department of Pharmaceutical Technology, Faculty of Chemistry and Pharmacy, University of Regensburg , 93040 Regensburg, Germany.
Susanne
S
Kirchhof
Department of Life Sciences, University of Trieste , Cattinara Hospital, Strada di Fiume 447, 34127 Trieste, Italy.
Michela
M
Abrami
Department of Pharmaceutical Technology, Faculty of Chemistry and Pharmacy, University of Regensburg , 93040 Regensburg, Germany.
Viktoria
V
Messmann
Department of Pharmaceutical Technology, Faculty of Chemistry and Pharmacy, University of Regensburg , 93040 Regensburg, Germany.
Nadine
N
Hammer
Department of Pharmaceutical Technology, Faculty of Chemistry and Pharmacy, University of Regensburg , 93040 Regensburg, Germany.
Achim M
AM
Goepferich
Department of Engineering and Architecture, University of Trieste , Piazzale Europa 1, 34127 Trieste, Italy.
Mario
M
Grassi
Department of Pharmaceutical Technology, Faculty of Chemistry and Pharmacy, University of Regensburg , 93040 Regensburg, Germany.
Ferdinand P
FP
Brandl
D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D000068258:Bevacizumab / Q000378:metabolism*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D003911:Dextrans / Q000378:metabolism*; D016503:Drug Delivery Systems; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000378:metabolism; D020100:Hydrogels / Q000737:chemistry*; D008301:Maleimides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry
D020533:Angiogenesis Inhibitors; D003692:Delayed-Action Preparations; D003911:Dextrans; D020100:Hydrogels; D008301:Maleimides; C015219:fluorescein isothiocyanate dextran; C043592:maleimide; D000068258:Bevacizumab; D011092:Polyethylene Glycols; D016650:Fluorescein-5-isothiocyanate
Diels−Alder; antibody; controlled release; hydrogel; mesh size