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Metal-Organic Framework Encapsulation Preserves the Bioactivity of Protein Therapeutics.
Wang, Congzhou; Sudlow, Gail; Wang, Zheyu; Cao, Sisi; Jiang, Qisheng; Neiner, Alicia; Morrissey, Jeremiah J; Kharasch, Evan D; Achilefu, Samuel; Singamaneni, Srikanth.
Afiliación
  • Wang C; Department of Mechanical Engineering and Materials Science, Institute of Materials Science and Engineering, Washington University in St. Louis, St. Louis, MO, 63130, USA.
  • Sudlow G; Department of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Wang Z; Department of Mechanical Engineering and Materials Science, Institute of Materials Science and Engineering, Washington University in St. Louis, St. Louis, MO, 63130, USA.
  • Cao S; Department of Mechanical Engineering and Materials Science, Institute of Materials Science and Engineering, Washington University in St. Louis, St. Louis, MO, 63130, USA.
  • Jiang Q; Department of Mechanical Engineering and Materials Science, Institute of Materials Science and Engineering, Washington University in St. Louis, St. Louis, MO, 63130, USA.
  • Neiner A; Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, 63110, USA.
  • Morrissey JJ; Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, 63110, USA.
  • Kharasch ED; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, 63110, USA.
  • Achilefu S; Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, 63110, USA.
  • Singamaneni S; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Adv Healthc Mater ; 7(22): e1800950, 2018 11.
Article en En | MEDLINE | ID: mdl-30369102
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estructuras Metalorgánicas / Insulina Límite: Animals Idioma: En Revista: Adv Healthc Mater Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estructuras Metalorgánicas / Insulina Límite: Animals Idioma: En Revista: Adv Healthc Mater Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania