Fabrication of antibody-loaded microgels using microfluidics and thiol-ene photoclick chemistry

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V
Manuel GregoritzaAchim M Goepferich

Abstract

Reducing burst effects, providing controlled release, and safeguarding biologics against degradation are a few of several highly attractive applications for microgels in the field of controlled release. However, the incorporation of proteins into microgels without impairing stability is highly challenging. In this proof of concept study, the combination of microfluidics and thiol-ene photoclick chemistry was evaluated for the fabrication of antibody-loaded microgels with narrow size distribution. Norbornene-modified eight-armed poly(ethylene glycol) with an average molecular mass of 10,000 Da, 20,000 Da, or 40,000 Da were prepared as macromonomers for microgel formation. For functionalization, either hydrolytically cleavable ester or stable amide bonds were used. A microfluidic system was employed to generate precursor solution droplets containing macromonomers, the cross-linker dithiothreitol and the initiator Eosin-Y. Irradiation with visible light was used to trigger thiol-ene reactions which covalently cross-linked the droplets. For all bond-types, molecular masses, and concentrations gelation was very rapid (< 20 s) and a plateau for the complex shear modulus was reached after only 5 min. The generated microgels had a rod-...Continue Reading

Citations

Apr 10, 2021·Chemical Reviews·Benjamin D FairbanksChristopher N Bowman
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Minjun ChenGoran T Vladisavljević
Jul 17, 2021·Global Challenges·Pantelitsa DimitriouDavid Barrow
Jul 31, 2021·ACS Applied Bio Materials·Paige J LeValleyApril M Kloxin

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