Enhancement of temozolomide stability by loading in chitosan-carboxylated polylactide-based nanoparticles

摘要

In the presented work, amphiphilic nanoparticles based on chitosan and carboxy-enriched polylactic acid have been prepared to improve the stability of the pro-drug temozolomide in physiological media by encapsulation. The carrier, with a diameter in the range of 150-180 nm, was able to accommodate up to 800 mu g of temozolomide per mg of polymer. The obtained formulation showed good stability in physiological condition and preparation media up to 1 month. Temozolomide loaded inside the carrier exhibited greater stability than the free drug, in particular in simulated physiological solution at pH 7.4 where the hydrolysis in the inactive metabolite was clearly delayed. CS-SPLA nanoparticles demonstrated a pH-dependent TMZ release kinetics with the opportunity to increase or decrease the rate. Mass spectroscopy, UV-Vis analysis, and in vitro cell tests confirmed the improvement in temozolomide stability and effectiveness when loaded into the polymeric carrier, in comparison with the free drug.