Background : Hepatic ischemia/reperfusion injury (IRI) represents a significant form of liver damage that can result in severe organ failure, often associated with procedures such as liver surgery, liver transplantation, and shock. This study outlines the formulation and characterization of lipid-polymer hybrid nanoparticles (LPHNPs) loaded with pterostilbene (PT). The nanoparticles were scrutinized for their effectiveness against hepatic injury induced by ischemia/reperfusion (IR), and the underlying mechanisms were evaluated.

Methods : Swiss Wistar rats were used in the study and PT-LPHNPs was orally given to the rats. The hepatic, non-hepatic, oxidative stress parameters, cytokines, inflammatory and apoptosis parameters were estimated. mRNA expression of apoptosis parameters were estimated. Immunohistochemical analysis for hepatic SMAD-4 and NF-κB was carried out in addition to histopathological investigation.

Results : The PT-LPHNPs exhibited the particle size (163.2 nm), entrapment efficiency (96.53%) and zeta potential (-0.660 mV). The TEM and photomicrograph images showed the dense spherical shape of optimized aforementioned formulation. PT-LPHNPs remarkably suppressed the level of hepatic parameters like AFP, AST, ALT, ALP; non-hepatic parameters such as TBL, GGT. PT-LPHNPs significantly (P<0.001) altered the level oxidative stress parameters viz., MDA< SOD, CAT, GSH, GPx; inflammatory cytokines like TNF-α, IL-1β, Il-6, IL-10, IL-18, IL-33; inflammatory parameters like COX-2, iNOS, VEGF, PGE2, NF-κB, respectively. PT-LPHNPs treatment remarkably suppressed the NF-κB and SMAD-4 protein expression. LPHNPs treatment remarkably altered the expression of Bax, Bcl-2 and caspase-3.

Conclusions : The current finding suggest that PT-LPHNPs possesses a potential effect against hepatic injury via alteration of Bcl-2/Bax and NF-κB/SMAD-4 pathways