title: A novel in-situ-gelling liquid suppository for site-targeting delivery of anti-colorectal cancer drugs.
abstract: In order to avoid anti-cancer drugs undergoing a first-pass effect and reduce their toxicity, and to solve conventional suppositories defects, we developed an in-situ-gelling and injectable Pluronic-poly(acrylic acid) (Pluronic-PAA) liquid suppository, which could gel fast in the physiological state and had suitable gel strength and bioadhesive force. The liquid suppositories were inserted into the rectum of rabbits without difficulty and leakage, and retained in the rectum for at least 6 h and while releasing the drug. The toxicity and cytotoxic tests indicated that Pluronic and PAA were non-toxic materials and could inhibit colon cancer cells when oxaliplatin was incorporated. C max and AUC0→12h values of oxaliplatin after rectal administration of a oxaliplatin suppository were higher than those for an oxaliplatin solution administered orally. These results suggest that an in-situ-gelling and injectable liquid suppository for humans can be further developed as a more convenient and effective rectal dosage form.
authors.affiliation: a Department of Chemical and Materials Engineering, Southern Taiwan University, Tainan 710, Taiwan. hrlin@mail.stut.edu.tw.
authors.forename: Hong-Ru
authors.initials: HR
authors.lastname: Lin
authors.forename: Chao-Chih
authors.initials: CC
authors.lastname: Tseng
authors.forename: Yiu-Jiuan
authors.initials: YJ
authors.lastname: Lin
authors.forename: Ming-Hung
authors.initials: MH
authors.lastname: Ling
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002460:Cell Line; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D065546:Drug Liberation; D005782:Gels / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D008297:Male; D008422:Materials Testing; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077150:Oxaliplatin; D011817:Rabbits; D051381:Rats; D012007:Rectum / Q000187:drug effects / Q000378:metabolism; D012996:Solutions / Q000737:chemistry; D013488:Suppositories / Q000737:chemistry / Q000633:toxicity; D013552:Swine; D014783:Viscosity
chemical_list: D000180:Acrylic Resins; D000970:Antineoplastic Agents; D005782:Gels; D009944:Organoplatinum Compounds; D012996:Solutions; D013488:Suppositories; D000077150:Oxaliplatin; C006903:carbopol 940