Ziegler, Christian E. and Graf, Moritz and Nagaoka, Makoto and Groner, Jonas and Mietzner, Raphael and Breunig, Miriam and Goepferich, Achim M. (2023) Injectable Anhydrous Poly(ethylene glycol) Polymer Liquids Form Protein Depot for Extended Controlled Release Applications Via Rapid In Situ Gelation. MOLECULAR PHARMACEUTICS, 20 (5). pp. 2465-2476. ISSN 1543-8384, 1543-8392
Full text not available from this repository. (Request a copy)Abstract
Water-free preparation of protein delivery systems has the potential to overcome the limitations of hydrogel depot systems such as off-target reactions, functional group hydrolysis, and limited loading capacity. However, a major roadblock in the development and use of these systems is administration as implantation is often required. In this study, we developed a biodegradable and water-free injectable protein delivery system via inverse electron demand Diels-Alder reaction between norbornene-and tetrazine-functionalized four-armed poly(ethylene glycol) macromonomers. 1:1 mixtures of these precursors gelled rapidly in situ, taking less than 11 s to reach their gelation point. Methyl substitution of tetrazine slowed the gelation time and increased the cross-linking density, whereas oxygen incorporation into norbornene changed the mechanical properties. Introduction of hydrolytically cleavable groups enabled biodegradability. Using phenyl carbamate and phenyl carbonate ester groups, we could tune the stability. Controlled release of the protein surrogate glucose oxidase was achieved over a period of 500 days. The novel preparation method presented here is a promising step toward the development of water-free injectable protein depots for controlled drug delivery.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DIELS-ALDER REACTIONS; DRUG-DELIVERY SYSTEMS; CROSS-LINKING; SUSTAINED-RELEASE; HYDROGELS; DEGRADATION; TIME; water-free; protein delivery system; in situ gelation; inverse electron demand Diels-Alder reaction; four-armed poly(ethylene glycol) |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Mar 2024 11:49 |
| Last Modified: | 09 Mar 2024 11:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/59320 |
Actions (login required)
 |
View Item |
