Continuous-flow synthesis of ZIF-8 biocomposites with tunable particle size

Abstract

Zeolitic Imidazolate Framework (ZIF) biocomposites show the capacity to protect and deliver bio-therapeutics. To date, the progress in this research area is based on laboratory batch methods. To further explore the potential of ZIF-biocomposites for application to biomedicine and biotechnology, the continuous production of ZIF-biocomposites of specific particle size is desirable. Here we report the first continuous flow synthetic method for the encapsulation of a model protein (bovine serum albumin, BSA) and a clinical therapeutic (α1-antitrypsin, AAT) in ZIF-8. We studied the in situ kinetics of nucleation, growth and crystallization of BSA@ZIF-8 by small angle X-ray scattering. By controlling the injection time of ethanol, we could quench the particle growth via ethanol-induced crystallization from amorphous particles to ZIF-8 crystals. The particle size of the biocomposite was tuned in the 40-100 nm range by varying residence time prior to introduction of ethanol. As a proof-of-concept, we used this protocol for the encapsulation of AAT in ZIF-8. Upon release of the bio therapeutic from the composite, the trypsin inhibitor function of AAT was preserved.