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To increase the antitumor activity of gemcitabine along with overcoming its important drawbacks (poor biological half-life and the induction of resistance), we investigated a colloidal carrier based on biodegradable poly(butylcyanoacrylate) nanoparticles. Two gemcitabine loading methods were extensively analyzed: (i) surface adsorption in already formed nanoparticles after incubation in a drug solution; and (ii) gemcitabine addition before the anionic emulsion/polymerization process of the butylcyanoacrylate monomer and subsequent drug trapping into the polymeric network. The latter yielded a higher gemcitabine loading and a sustained release profile. The main factors determining the gemcitabine entrapment into the polymer network and the release kinetic of gemcitabine were analyzed. The cytotoxicity of gemcitabine-loaded polymer was tested in sensitive murine leukemia L1210 wt cells, showing similar activity to the free drug. Following intravenous treatment of mice bearing aggressive leukemia L1210 wt subcutaneous tumors, gemcitabine-loaded poly(butylcyanoacrylate) nanoparticles displayed significantly greater antitumor activity compared to the free chemotherapy agent. This was confirmed by histology studies, suggesting the potential of this gemcitabine delivery system for the efficient treatment of cancer.

Engineering of Poly(butylcyanoacrylate) Nanoparticles for the Enhancement of the Antitumor Activity of Gemcitabine