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.