Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 59, Issue 21, Pages 8123-8127Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202000678
Keywords
flow chemistry; in situ SAXS; metal-organic frameworks; MOF biocomposites; particle size
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Funding
- European Union [801464]
- TU Graz [LP-03]
- European Research Council under the European Union's Horizon 2020 Program (FP/2014-2020)/ERC Grant [771834-POP-CRYSTAL]
- Austrian Research Promotion Agency FFG through the Austrian COMET Program by the Austrian Federal Ministry of Transport, Innovation and Technology (BMVIT) [862766]
- Austrian Federal Ministry of Science, Research and Economy (BMWFW)
- State of Styria (Styrian Funding Agency (SFG))
- Austrian Federal Ministry of Education, Science and Research
- TU Graz
- UNI Graz
- Anton Paar GmbH
- CERICERIC Consortium [20187103]
- ARC [DP170103531]
- University of Bologna
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Zeolitic imidazolate framework (ZIF) biocomposites show the capacity to protect and deliver biotherapeutics. To date, the progress in this research area is based on laboratory batch methods. Now, the first continuous flow synthetic method is presented for the encapsulation of a model protein (bovine serum albumin, BSA) and a clinical therapeutic (alpha 1-antitrypsin, AAT) in ZIF-8. The in situ kinetics of nucleation, growth, and crystallization of BSA@ZIF-8 were studied by small-angle X-ray scattering. By controlling the injection time of ethanol, the particle growth could be quenched by 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, this procedure was used for the encapsulation of AAT in ZIF-8. Upon release of the biotherapeutic from the composite, the trypsin inhibitor function of AAT was preserved.
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