Orally Delivered Decitabine Loaded PLGA Nanoparticles Combined with Docetaxel Supress Solid Tumours: an in vitro investigation

Docetaxel is one of the greatest chemotherapeutic agent used in the treatment of solid tumours. However, resistance to docetaxel is a major clinical issue, which obstacle to achieve long time survival for patients with advanced disease. The inherent presence or emergence of drug-resistant tumour clones confines its efficiency in the treatment of cancers. The understanding that epigenetic changes are prevalent in cancer and play a causative role in its biology has led to the development of new therapeutic approaches that target the epigenetic machinery. Exploiting the gene reactivation by using epigenetically acting agents in combination with cytotoxic therapies, is a strategy of huge clinical relevance. Decitabine (DEC) is one such epigenetic drug, but its major disadvantage is its low oral bioavailability. There is no oral dosage form available for DEC. Since PLGA has an advantage of overcoming acidic and enzymatic degradation, the present investigation was aimed at fabricating PLGA 50:50 nanoparticles of decitabine (DEC-NPs); and thereafter, examine a combination treatment in vitro and in vivo with docetaxel (DTX). DEC-NPs were formulated by spontaneous emulsification solvent diffusion technique. The optimized formulation had PS of 124.3 ± 4.2 nm, ZP of -23.2 ± 1.2 mV, and EE of 41.8 ± 4.3%. A comparative study indicated that the cytotoxicity of DTX and DEC combination on MCF-7 cells was significantly higher (p <0.05) than DTX and DEC alone.