Metal-Organic Framework Encapsulation Preserves the Bioactivity of Protein Therapeutics.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Wang, C; Sudlow, G; Wang, Z; Cao, S; Jiang, Q; Neiner, A; Morrissey, JJ; Kharasch, ED; Achilefu, S; Singamaneni, S

Published Date

  • November 2018

Published In

Volume / Issue

  • 7 / 22

Start / End Page

  • e1800950 -

PubMed ID

  • 30369102

Pubmed Central ID

  • PMC6453541

Electronic International Standard Serial Number (EISSN)

  • 2192-2659

Digital Object Identifier (DOI)

  • 10.1002/adhm.201800950

Language

  • eng

Conference Location

  • Germany