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

Author:

McGovern Megan K.12,Witt Emily12,Rhodes Ashley C.12,Kim Jinhee34,Feig Vivian R.456,Bi Jianling12,Cafi Arielle B.12,Hatfield Sam127,Nwosu Ikenna127,Byrne James D.12ORCID

Affiliation:

1. Department of Radiation Oncology University of Iowa Iowa City Iowa USA

2. Department of Biomedical Engineering University of Iowa Iowa City Iowa USA

3. Department of Pharmacology and Toxicology University of Toronto Toronto Ontario Canada

4. Division of Gastroenterology Brigham and Women's Hospital, Harvard Medical School Boston Massachusetts USA

5. Department of Mechanical Engineering Massachusetts Institute of Technology Cambridge Massachusetts USA

6. David H. Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology Cambridge Massachusetts USA

7. Carver College of Medicine University of Iowa Iowa City Iowa USA

Abstract

AbstractTumor 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 (O2‐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 O2‐GeMs have on the entrapment and delivery of oxygen. Using a Parr reactor, we fabricated solid O2‐GeMs using carbohydrate‐based formulations used in the confectionary industry. In evaluating solid O2‐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 O2‐GeMs, especially polycaprolactone, effectively prolonged the dissolution of the solid O2‐GeMs. In vivo evaluation confirmed robust insertion and positioning of O2‐GeMs in a malignant peripheral nerve sheath tumor, highlighting potential clinical applications.

Funder

National Institutes of Health

Prostate Cancer Foundation

U.S. Department of Defense

V Foundation for Cancer Research

Dr. Ralph and Marian Falk Medical Research Trust

Publisher

Wiley

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