Fabrication, optimization, and characterization of umbelliferone β-D-galactopyranoside-loaded PLGA nanoparticles in treatment of hepatocellular carcinoma: in vitro and in vivo studies

Abstract

Vikas Kumar,1 Prakash Chandra Bhatt,2 Mahfoozur Rahman,1 Gaurav Kaithwas,3 Hani Choudhry,4,5 Fahad A Al-Abbasi,4 Firoz Anwar,4 Amita Verma6 1Natural Product Drug Discovery Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, Uttar Pradesh, India; 2Centre for Advanced Research in Pharmaceutical Sciences, Microbial and Pharmaceutical Biotechnology Laboratory, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India; 3Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (Central University), Vidya Vihar, Rai Bareli Road, Lucknow, India; 4Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; 5Cancer Metabolism and Epigenetic Unit, King Fahd Center for Medical Research, King Abdulaziz University, Jeddah, Saudi Arabia; 6Bio-organic and Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, Uttar Pradesh, India Abstract: Umbelliferone β-D-galactopyranoside (UFG), isolated from plants, exhibits promising inhibitory action on numerous diseases. The present research was initiated to develop a suitable delivery system for UFG with an intention to enhance its therapeutic efficacy against diethyl nitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in Wistar rats. UFG-loaded polymeric nanoparticles prepared by sonication were scrutinized for average size, drug loading capacity, zeta potential, and drug release potency in animals. HCC cell lines HuH-7 and Hep G2 were used for in vitro cytotoxic investigation. Several hepatic, nonhepatic, antioxidant, and anti-inflammatory biochemical parameters were estimated to establish the anticancer potential of UFG nanoformulation. Microscopical and histopathological investigations were also undertaken to substantiate the results of our work. Umbelliferone β-D-galactopyranoside-loaded poly(d,l-lactide-co-glycolide) nanoparticles (UFG-PLGA-NP) with particle size of 187.1 nm and polydispersity index 0.16 were uniform in nature with 82.5% release of the total amount of drug after 48 h. Our study successfully established the development and characterization of UFG-PLGA-NP with noticeable effect against both in vivo and in vitro models. The anticancer potential of UFG-PLGA-NP was brought about by the management of DEN-induced reactive oxygen species generation, mitochondrial dysfunction, proinflammatory cytokines alteration, and induction of apoptosis. Positive zeta potential on the surface of UFG-PLGA-NP would have possibly offered higher hepatic accumulation of UFG, particularly in the electron-dense mitochondria organelles, and this was the take-home message from this study. Our results demonstrated that such polymer-loaded delivery systems of UFG can be a better option and can be further explored to improve the clinical outcomes against hepatic cancer. Keywords: hepatocellular carcinoma, umbelliferone β-D-galactopyranoside nanoparticles, diethyl nitrosamine, cytokines, oxidative stress 

Keywords

• Hepatocellular carcinoma
• Umbelliferone β-D-galactopyranoside nanoparticles
• diethyl nitrosamine
• cytokines
• oxidative stress.