Oral administration of decitabine nanoparticles effectively suppresses Nmu-induced leukaemia in Sprague-Dawley rats and arrests K562 cells in S-phase

Oral delivery of anticancer drugs has been an important topic of research in medicine for a decade. Unfortunately, most of the anticancer drugs, either old or novel, with high therapeutic efficacy, do not realize their full potential in the market. The epigenetic drug, decitabine (DEC), is one such potent hypomethylating agent, but its effect is temporary. The main reason is low oral bioavailability due to the gastrointestinal (GI) drug barrier and other instabilities. Therefore, it is commercially available as i.v. infusion to be used in hospital settings. We aimed to design and fabricate decitabine loaded PLGA nanoparticles (DEC-NPs) for potential oral delivery of DEC. The DEC-NPs were characterized by particle size, zeta potential, differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), and in vitro, ex-vivo and in vivo release studies. The efficacy of DEC-NPs was investigated in vitro in leukaemia cells, K562, and in vivo by NMU induced leukaemia model of male Sprague Dawley rats. The antiproliferative effect of DEC-NPs was significantly enhanced (p < 0.05) over DEC in K562 cells with a significantly prolonged (p < 0.05) cell cycle arrest in the S-phase. Upon oral administration, the WBC count was significantly reduced (p < 0.05) by DEC-NPs in rats compared to plain drug. The studies suggested that DEC-NPs have high potential for effective oral delivery of decitabine.