Systematic Screening of Different Polyglycerin-Based Dienophile Macromonomers for Efficient Nanogel Formation through
Alexander Oehrl1, Sebastian Schötz1, Rainer Haag1
1Institute for Chemistry and Biochemistry, Department of Biology, Chemistry, and Pharmacy, Freie Universität Berlin, Takustr 3, D-14195, Berlin, Germany.
Abstract:
Alternatives for strain-promoted azide-alkyne cycloaddition (SPAAC) chemistries are needed because of the employment of expensive and not easily scalable precursors such as bicyclo[6.1.0]non-4-yne (BCN). Inverse electron demand Diels Alder (iEDDA)-based click chemistries, using dienophiles and tetrazines, offer a more bioorthogonal and faster toolbox, especially in the biomedical field. Here, the straightforward synthesis of dendritic polyglycerin dienophiles (dPG-dienophiles) and dPG-methyl-tetrazine (dPG-metTet) as macromonomers for a fast, stable, and scalable nanogel formation by inverse nanoprecipitation is reported. Nanogel size-influencing parameters are screened such as macromonomer concentration and water-to-acetone ratio are screened. dPG-norbonene and dPG-cyclopropene show fast and stable nanogel formation in the size range of 40-200 nm and are thus used for the coprecipitation of the model protein myoglobin. High encapsulation efficiencies of more than 70% at a 5 wt% feed ratio are obtained in both cases, showing the suitability of the mild gelation chemistry for the encapsulation of small proteins.
