Docetaxel-dimer prodrug as a glutathione-responsive nano drug delivery system for improved chemotherapy

The introduction of nanoparticles into clinical environments has encountered many challenges, however efforts in this field continues as before. Drug delivery through dimeric prodrugs may be considered as a novel approach in this regard. In this study, self-assembled reduction responsive carrier free, docetaxel-dimer nanoparticles (DTX-dimer NPs) with resilient stability were prepared through nanoprecipitation method. High drug content was achieved due to utilizing drug molecules as a carrier and cargo at same time. The use of disulfide linker for the dimer preparation made it responsive to the high concentration of glutathione at the tumor environment. In vitro and in vivo analysis was performed to assay the efficiency of prepared nanoparticles. In vitro drug release showed no burst release with 60 % of drugs release in 48 h for DTX-dimer NPs. Dimer's selectivity index (SI) as a sign of systemic toxicity and safety was higher in cancer cells compared with normal cells. In vivo study was also performed to analyse the efficacy and safety of the DTX-dimer NPs. Mice weight and white blood cell count (WBC) were measured as toxic signs of docetaxel. This work reveals the significant potential of redox-responsive prodrug nanoparticles in combating cancer.