Microfluidic synthesis of trastuzumab-encapsulated pH-responsive ZIF-67 nanoparticles for targeted drug delivery

Microfluidic synthesis of ZIF-67 nanoparticles has emerged as a promising strategy for producing stable and monodisperse nanomaterials. These porous, pH-sensitive nanoparticles exhibit instability in acidic environments but remain stable in neutral and basic conditions. The precursors for ZIF-67 synthesis are water-soluble, enabling the use of water as a mediating solvent. Hence, they are highly suitable for drug delivery applications, eliminating concerns associated with toxic solvents commonly employed in pharmaceutical synthesis. This study describes a microfluidic chip designed based on a specific architecture (i.e., split-and-recombine) for the microfluidic synthesis of ZIF-67 nanoparticles using water as a green solvent, while simultaneously encapsulating trastuzumab. The primary objective is to investigate the design, fabrication, and application of a chip for synthesis and drug loading, capable of producing ZIF-67 nanoparticles with high encapsulation efficiency for largescale synthesis and implementation in drug delivery scenarios. The synthesized nanoparticles exhibited an average diameter of approximately 200 nm, with an encapsulation efficiency exceeding 90 %. Drug release profiles were evaluated at two pH values (i.e., 7.4 and 6.5) showing less than 50 % and about 78 % release, respectively, using the dialysis bag method and UV-VIS spectroscopy. Additionally, corresponding kinetic models were derived. Characterization techniques, including SEM, FTIR, and EDS, were employed to thoroughly analyze the synthesized materials.