Poly(alkylcyanoacrylate) colloidal particles as vehicles for antitumour drug delivery: a comparative study

Because of the fundamental importance of new therapeutic routes for cancer treatment, a number of systems based on colloidal particles as vehicles for the delivery of chemotherapeutic agents have been devised. The target is always to provide the proper dose of the antitumour agent only at the desired locus of action, thus reducing the unwanted side effects. The systems studied in this work are nanospheres of the biodegradable polymers poly(ethyl-2-cyanoacrylate), poly(butylcyanoacrylate), poly(hexylcyanoacrylate) and poly(octylcyanoacrylate), all suitable for parenteral administration, as vehicles for 5-fluorouracil, a well studied drug used for the treatment of solid tumours. Two loading methods have been analyzed: the first one is based on drug addition during the process of generation of the particles, by an anionic emulsion/polymerization procedure, and the subsequent drug trapping in the polymeric network. The second method is based on surface adsorption in already formed nanoparticles, after incubation in the drug solution. A detailed investigation of the capabilities of the polymer particles to load this drug is described. The main factors determining the drug incorporation to the polymer network were the type of monomer, the pH and the drug concentration. The release kinetics of 5-fluorouracil is found to be controlled by the pH of the release medium, the type of drug incorporation and the type of polymer.