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

Publication ,  Journal Article
Wang, C; Sudlow, G; Wang, Z; Cao, S; Jiang, Q; Neiner, A; Morrissey, JJ; Kharasch, ED; Achilefu, S; Singamaneni, S
Published in: Adv Healthc Mater
November 2018

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.

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Published In

Adv Healthc Mater

DOI

EISSN

2192-2659

Publication Date

November 2018

Volume

7

Issue

22

Start / End Page

e1800950

Location

Germany

Related Subject Headings

  • Temperature
  • Mice
  • Metal-Organic Frameworks
  • Liver
  • Insulin
  • Drug Stability
  • Drug Compounding
  • Diabetes Mellitus, Experimental
  • Circular Dichroism
  • Cell Survival
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wang, C., Sudlow, G., Wang, Z., Cao, S., Jiang, Q., Neiner, A., … Singamaneni, S. (2018). Metal-Organic Framework Encapsulation Preserves the Bioactivity of Protein Therapeutics. Adv Healthc Mater, 7(22), e1800950. https://doi.org/10.1002/adhm.201800950
Wang, Congzhou, Gail Sudlow, Zheyu Wang, Sisi Cao, Qisheng Jiang, Alicia Neiner, Jeremiah J. Morrissey, Evan D. Kharasch, Samuel Achilefu, and Srikanth Singamaneni. “Metal-Organic Framework Encapsulation Preserves the Bioactivity of Protein Therapeutics.Adv Healthc Mater 7, no. 22 (November 2018): e1800950. https://doi.org/10.1002/adhm.201800950.
Wang C, Sudlow G, Wang Z, Cao S, Jiang Q, Neiner A, et al. Metal-Organic Framework Encapsulation Preserves the Bioactivity of Protein Therapeutics. Adv Healthc Mater. 2018 Nov;7(22):e1800950.
Wang, Congzhou, et al. “Metal-Organic Framework Encapsulation Preserves the Bioactivity of Protein Therapeutics.Adv Healthc Mater, vol. 7, no. 22, Nov. 2018, p. e1800950. Pubmed, doi:10.1002/adhm.201800950.
Wang C, Sudlow G, Wang Z, Cao S, Jiang Q, Neiner A, Morrissey JJ, Kharasch ED, Achilefu S, Singamaneni S. Metal-Organic Framework Encapsulation Preserves the Bioactivity of Protein Therapeutics. Adv Healthc Mater. 2018 Nov;7(22):e1800950.
Journal cover image

Published In

Adv Healthc Mater

DOI

EISSN

2192-2659

Publication Date

November 2018

Volume

7

Issue

22

Start / End Page

e1800950

Location

Germany

Related Subject Headings

  • Temperature
  • Mice
  • Metal-Organic Frameworks
  • Liver
  • Insulin
  • Drug Stability
  • Drug Compounding
  • Diabetes Mellitus, Experimental
  • Circular Dichroism
  • Cell Survival