Controlled release of 5-fluorouracil or mitomycin-c from polymer matrix: Preparation by radiation polymerization and in vivo evaluation of the anticancer drug/polymer composites

Polymer tablets containing anticancer drugs such as 5-fluorouracil (5-FU) and mitomycin-C (MMC) have been prepared to evaluate the drug-release characteristics in vitro and the effect on local control of mouse solid tumors in vivo. Radiation-induced polymerization of hydrophilic monomers (2-hydroxyethyl methacrylate and related monomers) at low temperature (-80°C) was performed to immobilize 5-FU or MMC in the polymer matrix. The drug was dispersed as microcrystallines within the polymer matrix. The rate of drug release in vitro in buffer solution (pH7.0, 37°C) increased with increase in hydrophilicity of polymer matrix. Appropriate amount of crosslinks within the polymer matrix, as formed by ethylene glycol dimethacrylate (2G) added in the polymerization system, was effective to control the rate of drug release. The drug release became faster upon the addition of increasing amount of water in the radiation-induced polymerization. The tablet consisting of drug/polymer was buried surgically near solid tumors of striate muscle sarcoma (S180) transplanted to Kunming mice and the therapeutic effect of slow releasing drugs was evaluated in vivo by reference to intraperitoneal (i.p.) injection of the corresponding drugs. The slow releasing drugs led to high chemotherapeutic gain for local control of solid tumors with remarkable reduction of toxic side effect of the drugs.