Preparation, toxicity analysis and in vivo protective effect of phyllanthin-loaded PLGA nanoparticles against CCl4-induced hepatic fibrosis

Phyllanthin is a well-known hepatoprotective lignin from the plant Phyllanthus amarus (P. amarus). Its limited solubility in water makes is suitable candidate for nanoparticulate drug delivery system which can provide benefits of better absorption as well as increase the loading of the drug in water. The present investigation was carried out to synthesize phyllanthin nanoparticles (Phyll NP's) using poly lactic-co-glycolic acid (PLGA) as a polymer which is one of the most used biocompatible and biodegradable polymeric candidate with sustained drug release potential at desirable doses. The synthesized Phyll NP's were found to be of 187.6 nm ± 5.0 nm in size and were able to entrap 82.8%.± 1.88% of phyllanthin. Moreover, Transmission electron microscopy (TEM) revealed that the Phyll NP's were spherical in shape. Preclinical developmental toxicity of Phyll NP's in zebrafish embryo model. The in vivo anti-fibrotic efficacy of the Phyll NP's was evaluated in carbon tetrachloride (CCl4)-induced model of hepatic fibrosis by studying various biochemical parameters and also by performing masson's trichrome staining of liver tissue sections. Phyllanthin nanoparticles were found to combat CCl4-induced fibrosis and hepatotoxicity and were able to restore normalcy by reducing levels of liver marker enzymes and collagen levels in a dose dependent manner. The results of the present investigation revealed that Phyll NP's were found to possess higher anti-fibrotic effect at low doses due to an increase in aqueous drug loading in form of nanoparticulate system.