Development of rectal delivered thermo-reversible gelling film encapsulating a 5-fluorouracil hydroxypropyl-β-cyclodextrin complex

• HP-β-CD inclusion and thermo-reversible techniques were applied in combination.
• 5FU-HP-ß-CD complex increased drug solubility and facilitated drug transport.
• Thermo-reversible gel improved drug allocation and patient's compliance.
• The combination improved local drug concentration in respect to that in circulation.

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 100.4 M−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 10 h treatment period. Therefore, this HP-β-CD based formulation might improve the therapeutic effect of 5FU on colon-rectal cancer.