5-FU-hydrogel inhibits colorectal peritoneal carcinomatosis and tumor growth in mice.
BACKGROUND
Colorectal peritoneal carcinomatosis (CRPC) is a common form of systemic metastasis of intra-abdominal cancers. Intraperitoneal chemotherapy is a preferable option for colorectal cancer. Here we reported that a new system, 5-FU-loaded hydrogel system, can improve the therapeutic effects of intraperitoneal chemotherapy.


METHODS
A biodegradable PEG-PCL-PEG (PECE) triblock copolymer was successfully synthesized. The biodegradable and temperature sensitive hydrogel was developed to load 5-FU. Methylene blue-loaded hydrogel were also developed for visible observation of the drug release. The effects and toxicity of the 5-FU-hydrogel system were evaluated in a murine CRPC model.


RESULTS
The hydrogel system is an injectable flowing solution at ambient temperature and forms a non-flowing gel depot at physiological temperature. 5-FU-hydrogel was subsequently injected into abdominal cavity in mice with CT26 cancer cells peritoneal dissemination. The results showed that the hydrogel delivery system prolonged the release of methylene blue; the 5-FU-hydrogel significantly inhibited the peritoneal dissemination and growth of CT26 cells. Furthermore, intraperitoneal administration of the 5-FU-hydrogel was well tolerated and showed less hematologic toxicity.


CONCLUSIONS
Our data indicate that the 5-FU-hydrogel system can be considered as a new strategy for peritoneal carcinomatosis, and the hydrogel may provide a potential delivery system to load different chemotherapeutic drugs for peritoneal carcinomatosis of cancers.
Wang
Yongsheng
Y
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, China. wangys@scu.edu.cn
Gong
Changyang
C
Yang
Li
L
Wu
Qinjie
Q
Shi
Shuai
S
Shi
Huashan
H
Qian
Zhiyong
Z
Wei
Yuquan
Y
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016503:Drug Delivery Systems; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D020100:Hydrogels; D051379:Mice; D008807:Mice, Inbred BALB C; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D000964:Antimetabolites, Antineoplastic; D020100:Hydrogels; D011091:Polyesters; D011108:Polymers; C502908:poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol); D011092:Polyethylene Glycols; D005472:Fluorouracil