A novel anhydrous preparation of PEG hydrogels enables high drug loading with biologics for controlled release applications. (15th March 2021)

• Record Type: Journal Article
• Authors: Ziegler, Christian E.; Graf, Moritz; Beck, Sebastian; Goepferich, Achim M.
• Is Part Of: European polymer journal. Volume 147(2021)
• Publication Date: 2021-03-15
• Subjects: Water-free -- Melt polymerization -- Diels-Alder reaction -- Hydrogel -- Therapeutic protein delivery system; Polymers -- Periodicals; Polymerization -- Periodicals; Polymères -- Périodiques; Polymérisation -- Périodiques; Polymerization; Polymers; Periodicals; Electronic journals; 547.705
• DOI: 10.1016/j.eurpolymj.2021.110286
• Languages: English
• ISSNs: 0014-3057

Abstract

Graphical abstract: Highlights: Diels-Alder polymers represent an anhydrous preparation method for PEG hydrogels. Water absence prevents hydrolysis of maleimide groups. Proteins in solid state do not interact with polymer components. Diels-Alder polymers show high drug loading capacity. Glucose oxidase was released in a controlled manner over 100 days. Abstract: Hydrogels are very attractive materials to embed biologics for controlled release over long timescales. However, aqueous preparations pose certain obstacles regarding protein integrity, stability of functional groups, and loading capacity. To overcome these obstacles, the Diels-Alder reaction of furyl- and maleimide-functionalized eight-armed poly(ethylene glycol) (PEG) was used for the polymer preparation in the melt. The water-free reaction was investigated for protein interactions, protein- and maleimide group stability, and protein loading capacity. The melt polymerization was found to be highly protective against protein PEGylation and maleimide hydrolysis. The polymer gels were evaluated as a potential release system for biologics, achieving controlled release of the model protein glucose oxidase over a time period of 100 days. Furthermore, the loading could be increased to 15% (w/w) without influencing the release kinetics. This work represents a promising preparation method for degradable and water-free drug delivery systems that can be used to encapsulate biologics for controlled release.