3.8 Article

Self-Assembled, Dilution-Responsive Hydrogels for Enhanced Thermal Stability of Insulin Biopharmaceuticals

Journal

ACS BIOMATERIALS SCIENCE & ENGINEERING
Volume 7, Issue 9, Pages 4221-4229

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.0c01306

Keywords

supramolecular; drug delivery; biotherapeutic; cold chain; biomaterials; hydrogel

Funding

  1. NIDDK R01 (NIH) [R01DK119254]
  2. Stanford Diabetes Research Center (NIH) [P30DK116074]
  3. Center for Human Systems Immunology with Bill & Melinda Gates Foundation [OPP1113682]
  4. Bill & Melinda Gates Foundation [OPP1211043]
  5. Stanford Graduate Fellowship
  6. Tau Beta Pi Graduate Fellowship
  7. Caltech Summer Undergraduate Research Fellowship program
  8. NSERC Postgraduate Scholarship
  9. Stanford BioX Bowes Graduate Student Fellowship
  10. Novo Nordisk Foundation [NNF18OC0030896]
  11. Stanford Bio-X Program
  12. Department of Defense NDSEG Fellowship
  13. National Science Foundation Graduate Research Fellowship
  14. Gabilan Fellowship of the Stanford Graduate Fellowship in Science and Engineering
  15. Danish Council of Independent Research [DFF5054-00215]
  16. Bill and Melinda Gates Foundation [OPP1211043] Funding Source: Bill and Melinda Gates Foundation

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Hydrogels have the potential to effectively encapsulate and stabilize biotherapeutics, such as insulin, preventing issues caused by harsh conditions during storage and transportation. This supramolecular hydrogel system can maintain the bioactivity of insulin for over 28 days and can be easily recovered for administration at the point of care, showing promise in reducing the dependence of insulin and other biotherapeutics on the cold chain.
Biotherapeutics currently dominate the landscape of new drugs because of their exceptional potency and selectivity. Yet, the intricate molecular structures that give rise to these beneficial qualities also render them unstable in formulation. Hydrogels have shown potential as stabilizing excipients for biotherapeutic drugs, providing protection against harsh thermal conditions experienced during distribution and storage. In this work, we report the utilization of a cellulose- based supramolecular hydrogel formed from polymernanoparticle (PNP) interactions to encapsulate and stabilize insulin, an important biotherapeutic used widely to treat diabetes. Encapsulation of insulin in these hydrogels prevents insulin aggregation and maintains insulin bioactivity through stressed aging conditions of elevated temperature and continuous agitation for over 28 days. Further, insulin can be easily recovered by dilution of these hydrogels for administration at the point of care. This supramolecular hydrogel system shows promise as a stabilizing excipient to reduce the cold chain dependence of insulin and other biotherapeutics.

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