Poloxamer 188 and propylene glycol-based rectal suppository enhances anticancer effect of 5-fluorouracil in mice.
The tumoricidal and apoptosis-inducing activities of 5-fluorouracil (5-FU) have been demonstrated in experimental and clinical investigations. Clinically, the 5-FU suppository form has been widely adopted for its advantages of less systemic toxicity, higher local tissue concentrations, and reduced first-pass effect. In this study, we investigated the feasibility of rectal administration of 5-FU suppository based on poloxamer 188 (P188) and propylene glycol (PG) and its anticancer effect on the murine experimental cancer models. The rectal suppository was made with 70% P188 and 30% PG, which was a solid phase at room temperature and instantly melted at physiological temperature. The treatment with the 5-FU suppository was more effective than the oral route in decreasing the volume of rectal cancer in mice. In addition, the survival rate of the mice with rectal cancer was higher in the group treated with the 5-FU suppository than in the group treated with 5-FU orally. Furthermore, in mice skin cancers induced by inoculation of murine CT-26 colon carcinoma cells, the anticancer effect of 5-FU was significantly enhanced by the rectal administration of the suppository than by oral treatment. Taken together, the results suggest that a poloxamer gel system with 5-FU/P188/PG is an effective rectal dosage form for the treatment of both rectal and non-rectal cancers.
Paek
Seung-Hwan
SH
College of Pharmacy, Yeungnam University, Gyeongsan, Korea.
Xuan
Jing-Ji
JJ
Choi
Han-Gon
HG
Park
Byung Chul
BC
Lee
Yoon-Seok
YS
Jeong
Tae-Cheon
TC
Jin
Chun Hua
CH
Oh
Yu-Kyoung
YK
Kim
Jung-Ae
JA
D000285:Administration, Rectal; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D045744:Cell Line, Tumor; D005472:Fluorouracil / Q000008:administration & dosage* / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D014677:Pharmaceutical Vehicles; D020442:Poloxamer; D019946:Propylene Glycol; D012004:Rectal Neoplasms / Q000188:drug therapy; D012878:Skin Neoplasms / Q000188:drug therapy; D012995:Solubility; D013488:Suppositories
D000964:Antimetabolites, Antineoplastic; D014677:Pharmaceutical Vehicles; D013488:Suppositories; D020442:Poloxamer; D019946:Propylene Glycol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005472:Fluorouracil