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 <5min from a liquid at room temperature to a
hydrogel at body temperature. The
hydrogels released 50% of their payload within 30min 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 21days 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.