The clinical use of
5-fluorouracil, one of the drugs of choice in
colon cancer therapy, is limited by a nonuniform oral absorption, a short plasma half-life, and by the development of
drug resistances by malignant cells. We hypothesized that the formulation of biodegradable nanocarriers for the efficient delivery of this
antitumor drug may improve its
therapeutic effect against advanced or recurrent
colon cancer. Hence, we have engineered two 5-fluorouracil-loaded nanoparticulate systems based on the biodegradable
polymers poly(
butylcyanoacrylate) and poly(ε-
caprolactone).
Drug incorporation to the nanosystems was accomplished by entrapment (encapsulation/dispersion) within the polymeric network during nanoparticle synthesis, i.e., by anionic polymerization of the monomer and interfacial
polymer disposition, respectively. Main factors determining
5-fluorouracil incorporation within the polymeric nanomatrices were investigated. These nanocarriers were characterized by high
drug entrapment efficiencies and sustained drug-release profiles. In vitro studies using human and murine
colon cancer cell lines demonstrated that both types of nanocarriers significantly increased the antiproliferative effect of the encapsulated
drug. In addition, both nanoformulations produced in vivo an intense
tumor growth inhibition and increased the mice survival rate, being the greater
tumor volume reduction obtained when using the poly(ε-
caprolactone)-based formulation. These results suggest that these nanocarriers may improve the antitumor activity of
5-fluorouracil and could be used against advanced or recurrent
colon cancer.