Abstract
This study describes the development and characterization of caffeic acid (CA)-loaded lipid polymer hybrid nanoparticles (LPHNPs) for treating liver cirrhosis. The developed CA-loaded LPHNPs showed particle size of 150.9 nm, zeta potential of - 0.660 mV, and entrapment efficiency of 95.12%. The photomicrograph and TEM images revealed a dense spherical shape of optimized aforementioned formulation. The in vitro drug release studies revealed cumulative CA release of 82.46% at the end of 80 h, while Korsemeyer-Peppas model was found to be best fitted (n < 0.45). Further, the stability testing at 25oC/60%RH revealed stable nanoparticles formulation with particle size homogeneity up to 12 weeks. Pharmacokinetic data revealed 6.1-fold higher bioavailability of CA-LPHNPs as compared to that of CA suspension. The biodistribution profile of CA-LPHNPs revealed higher concentrations in liver > spleen > kidney > heart > lung over the CA suspension. The CA-loaded LPHNPs found a reduction of hepatic enzymes including ALT, AST and ALP to the value quite close to the normal control group of rats. On the other side, the administration of CA-loaded LPHNPs resulted in normalization of the antioxidant value and reduced proinflammatory cytokines close to the normal control group of rats over the PCM induced liver cirrhosis group in rats. It was further established by histopathology of the liver microtome sections that the therapy affected liver cirrhosis.