Affiliation:
1. Department of Pharmaceutics Ghent University Ottergemsesteenweg 460 9000 Ghent Belgium
2. Polymer Chemistry Research group Centre of Macromolecular Chemistry (CMaC) Department of Organic and Macromolecular Chemistry Ghent University Krijgslaan 281, S4-bis 9000 Ghent Belgium
3. Department of Veterinary and Biosciences Ghent University Heidestraat 19 9820 Merelbeke Belgium
Abstract
AbstractPolyethylene glycol (PEG) is considered as the gold standard for colloidal stabilization of nanomedicines, yet PEG is non‐degradable and lacks functionality on the backbone. Herein, we introduce concomitantly PEG backbone functionality and degradability via a one‐step modification with 1,2,4‐triazoline‐3,5‐diones (TAD) under green light. The TAD‐PEG conjugates are degradable in aqueous medium under physiological conditions, with the rate of hydrolysis depending on pH and temperature. Subsequently, a PEG‐lipid is modified with TAD‐derivatives and successfully used for messenger RNA (mRNA) lipid nanoparticle (LNP) delivery, thereby improving mRNA transfection efficiency on multiple cell cultures in vitro. In vivo, in mice, mRNA LNP formulation exhibited a similar tissue distribution as common LNPs, with a slight decrease in transfection efficiency. Our findings pave the road towards the design of degradable, backbone‐functionalized PEG for applications in nanomedicine and beyond.
Funder
Fonds Wetenschappelijk Onderzoek