Nanoparticle based apigenin delivery intended to control hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the major causes of cancer related death globally. Apigenin (API) is a bioactive dietary flavonoid found in various common vegetables and fruits. It showed effective chemo-preservative and tumor-suppressive activity against many kinds of malignancies including HCC in-vitro. Here we have developed and characterized PLGA nanoparticles loaded with API (ApNp) and modified the required parameters for a successful parenteral delivery of apigenin to treat hepatocellular carcinoma in-vitro and in-vivo. Particle size was optimized according to the need for delivery in hepatic tissues. Surface morphology were engineered to increase the bioavailability of apigenin and to ensure the sustained drug release in the target site for a prolonged time. The cytotoxic effects of ApNp as well as API were tested against two human hepatocellular cancer cell lines, HepG2 and Huh-7. Cellular uptakes of nanoparticles were also investigated by confocal microscopy and fluorescence activated cell sorting. Biodistribution and bioavailability of API and ApNp were measured by bio-imaging and pharmacokinetic studies in-vivo. Further, to observe the tumor suppressive and anti-proliferative effect of API and ApNp, a HCC animal model was prepared and treated with API/ApNp and compared all the data with normal and untreated group of animals. Marker enzyme assays, macroscopic observation and histopathology investigation were done to establish the outcome of this work. Apigenin loaded nanoparticles had a sustained drug release pattern and successfully reached the hepatic cancer cells in-vitro as well as in liver of carcinogenic animals. ApNp predominantly delayed the progress of HCC in chemically induced rats. Quantification of apigenin by liquid chromatography-mass spectroscopy (LC-MS/MS) showed that apigenin availability significantly increased in blood and liver upon ApNp treatment. Targeted delivery of apigenin loaded nanoparticles substantially controlled the severity of hepatocellular carcinoma.