Metal-Organic Framework Encapsulation Preserves the Bioactivity of Protein Therapeutics

Congzhou Wang, Gail Sudlow, Zheyu Wang, Sisi Cao, Qisheng Jiang, Alicia Neiner, Jeremiah J. Morrissey, Evan D. Kharasch, Samuel Achilefu, Srikanth Singamaneni

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Protein therapeutics are prone to lose their structure and bioactivity under various environmental stressors. This study reports 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 analyses 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) is evaluated in vivo using a diabetic mouse model, and shows comparable bioactivity to refrigeration-stored insulin (−20 °C). It is also demonstrated that ZIF-8-preserved insulin has low cytotoxicity in vitro and does 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.

Original languageEnglish
Article number1800950
JournalAdvanced Healthcare Materials
Volume7
Issue number22
DOIs
StatePublished - Nov 21 2018

Keywords

  • insulin
  • preservation
  • protein therapeutics
  • resource-limited settings
  • zeolitic imidazolate framework-8

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