Graf, Moritz and Ziegler, Christian E. and Gregoritza, Manuel and Goepferich, Achim M. (2019) Hydrogel microspheres evading alveolar macrophages for sustained pulmonary protein delivery. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 566. pp. 652-661. ISSN 0378-5173, 1873-3476
Full text not available from this repository. (Request a copy)Abstract
Pulmonary delivery is a highly attractive alternative to injections for biologics such as therapeutic proteins. However, bioavailabilities generally suffer from the presence of phagocytic cells that clear particulate matter entering the lung. In this study, microgel particles were developed using an all-aqueous two-phase system approach and evaluated for their efficacy as an inhalable controlled release system. Norbornene- and thiol-modified four- and eight-armed poly (ethylene glycol) with an average molecular mass of 10,000 Da were prepared as macromonomers for microgel formation. Emulsions of precursor solution droplets containing macromonomers and Irgacure 2959 as photocatalyst were prepared in a dextran solution. Irradiation with UV light was used to covalently crosslink the droplets by triggering the thiol-ene reaction. The resulting microgels were processed to dry powder inhaler formulations, and respirable aerodynamic sizes were assessed in vitro. Microgels were loaded with the model proteins lysozyme and bovine serum albumin, with encapsulation efficiencies of 51.5% and 73.6%, respectively. Depending on the macromonomer type, protein-loaded microgels released their cargo over a 6-14 day period. In an MTT assay, the particles did not show significant cytotoxicity, and their recognition by alveolar macrophages was considerably lower than for polystyrene control particles. This makes the microgels a promising pulmonary delivery system for proteins and other biologics.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | POLY(ETHYLENE GLYCOL); THERAPEUTIC PROTEINS; POLYMER MICROSPHERES; CONTROLLED-RELEASE; RESPIRATORY-TRACT; PARTICLES; DEPOSITION; MICROGELS; SIZE; MICROPARTICLES; Aqueous two-phase system; Thiol-ene; Controlled release; Inhalation; Protein delivery; Hydrogel; Click chemistry |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Apr 2020 12:06 |
| Last Modified: | 02 Apr 2020 12:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26616 |
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