Pre‐Clinical Investigation of Repaglinide Nanoparticles in High Fat Diet with streptozotocin induced memory impaired rats

Background Diabetes Mellitus is a metabolic disorder characterized by insulin resistance with several abnormalities which trigger neuronal complications, neurodegeneration, and cognitive impairments. Repaglinide (REP) an insulinotropic, neuroprotective agent short-action poor absorption characteristics. Hence, the present study was aimed to investigate efficacy of REP-loaded lipid polymer-hybrid nanoparticles (REP-LPHNPs) in High Fat Diet low dose Streptozotocin (HFD-STZ) induced deficits wistar rats model. Methods The REP-LPHNPs were prepared solvent evaporation method. optimization statistical analysis LPHNPs done using Design-Expert software response surface Box-Behnken design. Animals fed HFD-STZ (30 mg/kg; i.p) induce impairment. Treatment carried out for 28 days separate groups viz, negative control, positive pure REP (4 mg/kg, p.o.), p.o.). Behavior assessment parameters like passive avoidance test, spatial navigation task, probe trial, spontaneous locomotor activities performed. Further, biochemical performed oxidative stress markers. Moreover, pharmacokinetic (PK) performed, assessed Phoenix WinNolin CerteraTM (Pharsight, U.S.A; version:8.0) non-compartmental modelling. Results having phospholipid coated hydrophobic polymer core successfully thoroughly. showed improved PK parameters, e.g., t1/2 (h) AUC, found increased twice than REP. significantly reduced impairment assessing behavioral tests. It observed that nanocarrier learning memory as compared Conclusion In summary, downsides loading into LPHNPs. demonstrates better effects alone HFD STZ encountered rats.