Continuous‐Flow Synthesis of ZIF‐8 Biocomposites with Tunable Particle Size

Abstract

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.

Stabilization of Supramolecular Membrane Protein-Lipid Bilayer Assemblies Through Immobilization in a Crystalline Exoskeleton

“…The initial formation of an amorphous phase is consistent with what we have observed with viral nanoparticles and other proteins. 30,42,44 Importantly, compared to the control samples, we observed faster crystallization for Lp@ZIF particles (e.g. 20×16 Lp@ZIF crystallization is 15 times faster than the pure ZIF-L particles; Figures S16-S19).…”

“…Kinetics of nucleation, particle growth, 38 crystallization, and the morphology of the particles were investigated in situ via synchrotron-based small-angle and wide-angle X-ray scattering (SAXS/WAXS) techniques. 42,43 We investigated four different samples (20×16 Lp@ZIF, 20×16 ZIF-L, 40×16 Lp@ZIF, and 40×16 ZIF-L) using a stopped flow device to initiate the rapid mixing of the reagents (mixing time <100 ms). See the SAXS section of the SI for full experimental details.…”

Metal–organic frameworks (MOFs) as host materials for the enhanced delivery of biomacromolecular therapeutics

“…This is because the conditions for synthesizing the MOF must be mild (e.g., low temperature, organic solvents) to ensure that the bioactivity of biomacromolecules is not compromised during the encapsulation process. [35][36][37][38] The above-mentioned conditions hamper the use of a significant number of available MOFs. Furthermore, since in-situ generation results in the the complete encapsulation of the biomacromolecule within the MOFs, the loaded biomacromolecules can only be released when the MOFs are decomposed.…”

Prospects of Exploring the Metal–Organic Framework for Combating Antimicrobial Resistance

“…A MOF with a large surface area and pore size allows more drugs to be conjugated to the surface and/or encapsulated, for efficient therapeutic action . Several researchers have exclusively worked on MOF size determination using various physical characterization tools including XRD, AFM, electron microscopy, fluorescence correlation spectroscopy, and dynamic light scattering. − Moreover, MOF has a net positive charge most often due to the metal element in the framework structure . This positive charge offers better interaction with negatively charged bacterial membranes.…”