Design, preparation, characterization, and evaluation of NR4A1 agonist novel 6-mercaptopurine monohydrate loaded nanostructured lipid carriers suspension for enhanced solubility and invivo bioavailability

6-Mercaptopurine (6-MP) is a prodrug widely used in the treatment of cancer, immunosuppressive agents, inflammatory bowel disease i.e. ulcerative colitis and Crohn’s disease. However, there are certain drawbacks; it is extremely low solubility in water because of extensive first pass metabolism by hepatic and intestinal enzymes and high affinity for the P-glycoprotein efflux mechanism. Consequently, its oral bioavailability is quite low. In this investigation, compritol® 888 ATO and oleic acid were chosen to represent liquid and solid lipids, respectively, to progress 6-MP-NLC (NLC-Nanostructured Lipid Carrier). 6-MP was effectively incorporated within NLC (6-MP-NLC) to boost the drug’s oral bioavailability. 6-MP-NLC was formulated utilising a modified melt-emulsification technique, additionally, the physicochemical characteristics were outlined. The evolved 6-MP-NLC drug formulation revealed in nanometric dimensions (124.5±2.3 nm), polydispersity index (PDI) (0.386±0.011), zeta potential (25.5±0.64mV), and high encapsulation efficiency (87.33 ± 0.08%). Moreover, it had a nearly spherical shape when viewed under the transmission electron microscope. Results from the differential scanning calorimeter and X-ray diffraction of 6-MP-NLC showed that the 6-MP crystal might be converted to an amorphous state. 6-MP-NLCs demonstrated a burst release, followed by a sustained release phase, according to the in vitro release profile. The cell viability assay for apoptosis showed that 6-MP-NLCs increased the cytotoxicity of A549 cells in vitro. The study found that oral administration of 6-MP-NLC significantly improved tmax (h). However, it did not significantly alter Cmax compared to the 6-MP oral suspension. Furthermore, nanostructured lipid carriers significantly enhance the effectiveness of 6-MP medications with low oral bioavailability.