Abstract
Methotrexate (MTX) widely used in the treatments of various types of malignancies, but high toxicity and short plasma half-life have limited its use. This study was aimed at developing a polymeric drug delivery system for improving the therapeutic index of this potent drug. To achieve these goals, PLGA and PLGA-PEG nanoparticles were prepared using the emulsification-solvent diffusion technique and were optimized for particle size and entrapment efficiency. The optimum loaded nanoparticles were evaluated by cytotoxicity and their ability to induce apoptosis compared to free drug by examining of caspase-3 activity. The results showed that optimized particles were 182 ± 14 nm and 258 ± 10 nm in size for PLGA-PEG and PLGA nanoparticles, respectively, with an entrapment efficiency of more than 51%. The cytotoxicity experiment showed that the nanoparticles were more effective than pure MTX and increase the activity of caspase-3 in MCF7 and AGS and A549 cell lines.
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