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Impact of formulation on solid oxygen-entrapping materials to overcome tumor hypoxia.

Megan K McGovernEmily WittAshley C RhodesJinhee KimVivian R FeigJianling BiArielle B CafiSam HatfieldIkenna NwosuJames D Byrne
Published in: Journal of biomedical materials research. Part A (2024)
Tumor hypoxia, resulting from rapid tumor growth and aberrant vascular proliferation, exacerbates tumor aggressiveness and resistance to treatments like radiation and chemotherapy. To increase tumor oxygenation, we developed solid oxygen gas-entrapping materials (O 2 -GeMs), which were modeled after clinical brachytherapy implants, for direct tumor implantation. The objective of this study was to investigate the impact different formulations of solid O 2 -GeMs have on the entrapment and delivery of oxygen. Using a Parr reactor, we fabricated solid O 2 -GeMs using carbohydrate-based formulations used in the confectionary industry. In evaluating solid O 2 -GeMs manufactured from different sugars, the sucrose-containing formulation exhibited the highest oxygen concentration at 1 mg/g, as well as the fastest dissolution rate. The addition of a surface coating to the solid O 2 -GeMs, especially polycaprolactone, effectively prolonged the dissolution of the solid O 2 -GeMs. In vivo evaluation confirmed robust insertion and positioning of O 2 -GeMs in a malignant peripheral nerve sheath tumor, highlighting potential clinical applications.
Keyphrases
  • peripheral nerve
  • drug delivery
  • radiation therapy
  • squamous cell carcinoma
  • signaling pathway
  • high dose
  • low dose
  • endothelial cells
  • locally advanced
  • soft tissue
  • blood flow