Folate receptor targeted 17-allylamino-17-demethoxygeldanamycin (17-AAG) loaded polymeric nanoparticles for breast cancer

Low water solubility and hepatotoxicity limited the clinical use of 17-allylamino-17-demethoxy geldanamycin (17-AAG), an inhibitor of heat shock protein 90 (HSP90). Folate targeted polylactide-co-glycolide–polyethylene glycol–folic acid (PLGA–PEG–FA) nanoparticles containing 17-AAG were prepared and characterized. Cellular uptake and in vitro cytotoxicity of the prepared nanoparticles were determined in MCF-7 human breast cancer cells. The particle size of 17-AAG loaded folate targeted nanoparticles was 238.67 ± 3.52 nm, drug loading was 8.25 ± 2.49% and about 80% of drug was released from the nanoparticles over 10 days. Cellular uptake studies showed much higher intracellular uptake of folate targeted nanoparticle as compared to nontargeted nanoparticles. Cytotoxicity study showed 2 fold increase (P < 0.05, n = 3) in the cytotoxicity of folate targeted nanoparticle in comparison to free drug or nontargeted nanoparticles. Due to their targeting ability, nanometer size, high drug loading and controlled release behavior, 17-AAG loaded PLGA–PEG–FA nanoparticles might be developed as a targeted delivery system for breast and other cancer treatment.

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► We prepared and characterized PLGA-PEG-FA nanoparticles containing 17-AAG.
► The nanoparticles showed sustained release of 17-AAG for more than 10 days.
► The targeted nanoparticlesshowed higher cellular uptake in breast cancer cells.
► The targeted nanoparticles showed increased cytotoxicity to the breast cancer cells.
► The nanoparticles seem to be suitable for targeting breast and other cancers.