Kirchhof, Susanne and Abrami, Michela and Messmann, Viktoria and Hammer, Nadine and Goepferich, Achim M. and Grassi, Mario and Brandl, Ferdinand P. (2015) Diels-Alder Hydrogels for Controlled Antibody Release: Correlation between Mesh Size and Release Rate. MOLECULAR PHARMACEUTICS, 12 (9). pp. 3358-3368. ISSN 1543-8384,
Full text not available from this repository. (Request a copy)Abstract
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 (xi) 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 (xi(avg)) 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 xi(avg). 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 (R-h), the time-dependent increase of xi(avg) 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 R-h < xi(avg). However, significant deviations from the theoretical predictions were observed when R-h >= xi(avg), most likely due to the statistical distribution of xi 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 xi and the release rate could facilitate the design of controlled release systems for antibodies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | POLY(ETHYLENE GLYCOL) HYDROGELS; OBSTRUCTION-SCALING MODEL; MACULAR DEGENERATION; POLYVINYL-ALCOHOL) HYDROGELS; PROTEIN DELIVERY; NMR; DIFFUSION; NETWORKS; CRYSTALLIZATION; SPECTROSCOPY; Diels-Alder; hydrogel; mesh size; controlled release; antibody |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Jun 2019 13:24 |
| Last Modified: | 12 Jun 2019 13:24 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4919 |
Actions (login required)
 |
View Item |
