Journal
JOURNAL OF CONTROLLED RELEASE
Volume 263, Issue -, Pages 46-56Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2017.02.025
Keywords
Semi-synthetic glycosaminoglycan (GAG); Radiation-induced proctitis; Silk-elastinlike protein polymer (SELP); Radiation Enteropathy; Hyaluronic acid; Colitis
Funding
- Huntsman Cancer Institute [P30 CA042014]
- National Institutes of Health [R01CA107621]
- University of Utah
- National Science Foundation [1256065]
- Division Of Graduate Education
- Direct For Education and Human Resources [1256065] Funding Source: National Science Foundation
Ask authors/readers for more resources
Radiation-induced proctitis (RIP) is the most common clinical adverse effect for patients receiving radiotherapy as part of the standard course of treatment for ovarian, prostate, colon, and bladder cancers. RIP limits radiation dosage, interrupts treatment, and lowers patients' quality of life. A prophylactic treatment that protects the gastrointestinal tract from deleterious effects of radiotherapy will significantly improve patient quality of life and may allow for higher and more regular doses of radiation therapy. Semi-synthetic glycosaminoglycan (GAG), generated from the sulfation of hyaluronic acid, are anti-inflammatory but have difficulty achieving therapeutic levels in many tissues. To enhance the delivery of GAG, we created an in situ gelling rectal delivery system using silk-elastinlike protein polymers (SELPs). Using solutions of SELP 815K (which contains 6 repeats of blocks comprised of 8 silk-like units, 15 elastin-like units, and 1 lysine-substituted elastin-like unit) with GAG GM-0111, we created an injectable delivery platform that transitioned in <5 min from a liquid at room temperature to a hydrogel at body temperature. The hydrogels released 50% of their payload within 30 min and enhanced the accumulation of GAG in the rectum compared to traditional enema-based delivery. Using a murine model of radiation-induced proctitis, the prophylactic delivery of a single dose of GAG from a SELP matrix administered prior to irradiation significantly reduced radiation-induced pain after 3, 7, and 21 days by 53 +/- 4%, 47 +/- 10%, and 12 +/- 6%, respectively. Matrix-mediated delivery of GAG by SELP represents an innovative method for more effective treatment of RIP and promises to improve quality of life of cancer patients by allowing higher radiotherapy doses with improved safety. (C) 2017 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available