Microfluidic Synthesis of a Bioactive Metal–Organic Framework for Glucose-Responsive Insulin Delivery

In the current study, we report the microfluidic synthesis of a metal-organic framework (MOF) for insulin delivery based on the stimulus response of glucose. Insulin- and gold nanoparticle (AuNP)-encapsulated zeolitic imidazolate framework-8 (ZIF-8) was synthesized using a continuous-flow, microfluidic mixing system via a single-step process. Glucose oxidase mimicking the activity of AuNPs was utilized for oxidizing glucose molecules that entered the porous ZIF-8. The AuNPs oxidized glucose into gluconic acid and hydrogen peroxide inside the MOF (Ins-AuNP-ZIF-8). The resulting acidic pH led to the disruption of ZIF-8 and released insulin. Thus, the presence of glucose molecules provided a stimulus for insulin release. The bioactive MOFs were characterized for the presence of functional groups, morphology, crystallinity, size, and elemental confirmation. The presence of fluorescein-5-isothiocyanate-labeled insulin in the composite was confirmed using confocal laser scanning microscopy. The loading of insulin per unit weight of the MOF, determined by size-exclusion-high-performance liquid chromatography, was 77 and 88% in the batch and microfluidic processes, respectively. Drug release studies confirmed the response of the MOFs to glucose, which triggered insulin release. The synthesis process did not affect the characteristics and application of ZIF-8 and Ins-AuNP-ZIF-8. This study involving the facile synthesis of bioactive MOFs offers a sustainable strategy to design stimulus-responsive drug delivery systems and could be exploited for biosensing applications.