Metal-organic Framework Encapsulation Preserves the Bioactivity of Protein Therapeutics

摘要

Protein therapeutics are prone to lose their structure and bioactivity under various environmental stressors. Herein, we report a facile approach using a nanoporous material, zeolitic imidazolate framework-8 (ZIF-8), as an encapsulant for preserving the prototypic protein therapeutic, insulin, against different harsh conditions that may be encountered during storage, formulation and transport, including elevated temperatures, mechanical agitation and organic solvent. Both immunoassay and spectroscopy analysis demonstrate the preserved chemical stability and structural integrity of insulin offered by the ZIF-8 encapsulation. Biological activity of ZIF-8 preserved insulin after storage under accelerated degradation conditions (i.e. 40°C) was evaluated in vivo using a diabetic mouse model, and showed comparable bioactivity to refrigeration-stored insulin (−20°C). We also demonstrate that ZIF-8 preserved insulin had low cytotoxicity in vitro and did not cause side effects in vivo. Furthermore, ZIF-8 residue can be completely removed by a simple purification step before insulin administration. This biopreservation approach is potentially applicable to diverse protein therapeutics, thus extending the benefits of advanced biologics to resource-limited settings and underserved populations/regions.