Institute of Physical and Theoretical Chemistry, Graz University of Technology, Stremayrgasse 9, 8010, Graz, Austria.
Center for Continuous Flow Synthesis and Processing (CCFLOW), Research Center Pharmaceutical Engineering GmbH (RCPE), Inffeldgasse 13, 8010, Graz, Austria.
Angew Chem Int Ed Engl. 2020 May 18;59(21):8123-8127. doi: 10.1002/anie.202000678. Epub 2020 Mar 17.
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 (α1-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.
沸石咪唑骨架（ZIF）生物复合材料具有保护和输送生物治疗剂的能力。迄今为止，该研究领域的进展基于实验室批量方法。现在，首次提出了一种连续流动合成方法，用于封装模型蛋白（牛血清白蛋白，BSA）和临床治疗药物（α1-抗胰蛋白酶，AAT）的 ZIF-8。通过小角 X 射线散射研究了 BSA@ZIF-8 的成核、生长和结晶的原位动力学。通过控制乙醇的注入时间，通过乙醇诱导的无定形颗粒向 ZIF-8 晶体的结晶，可以使颗粒生长猝灭。通过改变引入乙醇之前的停留时间，将生物复合材料的粒径调至 40-100nm 范围内。作为概念验证，该方法用于封装 AAT 在 ZIF-8 中。从复合材料中释放生物治疗药物后，AAT 的胰蛋白酶抑制剂功能得以保留。
