title: Development of rectal delivered thermo-reversible gelling film encapsulating a 5-fluorouracil hydroxypropyl-β-cyclodextrin complex.
abstract: We have developed a novel 5-Fluorouracil (5FU) formulation for rectal application to improve its therapeutic efficiency in colorectal cancer. The results indicated that 5FU formed an inclusion complex with Hydroxypropyl-β-Cyclodextrin (HP-β-CD). The stoichiometry of the complex was 1:1, with apparent stability constant of 100.4M(-1). After investigating physicochemical properties of the 5FU-HP-β-CD complex encapsulated with thermo-reversible gelling film, the optimized formulation P407/P188/HPMC/5FU-HP-β-CD (18.5/2.5/0.2/15%) was selected and evaluated. The result showed that the 5FU-HP-β-CD complex increased the solubility of 5FU, prolonged and enhanced its releasing. As compared to the raw drug, the transport efficiency of the 5FU-HP-β-CD complex itself or entrapped in thermo-reversible gelling film were respectively 7.3- and 6.8-fold increased, and the cellular uptake of 5-FU 4.9- and 5.4-fold elevated. There was no irritation or damage to rectal sites in the 10h treatment period. Therefore, this HP-β-CD based formulation might improve the therapeutic effect of 5FU on colon-rectal cancer.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People's Republic of China.
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Wang
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People's Republic of China.
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: Zheng
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People's Republic of China.
authors.forename: Shao-Hua
authors.initials: SH
authors.lastname: Chen
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People's Republic of China. Electronic address: hanyanxing@imm.ac.cn.
authors.forename: Yan-Xing
authors.initials: YX
authors.lastname: Han
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People's Republic of China. Electronic address: jiang.jdong@163.com.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Jiang
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D018938:Caco-2 Cells; D002152:Calorimetry, Differential Scanning; D005472:Fluorouracil / Q000008:administration & dosage* / Q000737:chemistry*; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D011817:Rabbits; D012007:Rectum / Q000378:metabolism*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D005472:Fluorouracil
keywords: 5FU; Colorectal cancer; HP-β-CD; Releasing; Thermo-reversible