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

• DOI: 10.2147/ijn.s136629
• Publication Date: 2017-09-11T20:22:19Z
• Authors: Vikas Kumar; Prakash Bhatt; Mahfoozur Rahman; Gaurav Kaithwas; Hani Choudhry; Fahad Al-Abbasi; Firoz Anwar; Amita Verma
• Keywords: Male; Medicine (General); Carcinoma, Hepatocellular; Hepatocellular carcinoma; Apoptosis; 03 medical and health sciences; R5-920; Drug Delivery Systems; Polylactic Acid-Polyglycolic Acid Copolymer; International Journal of Nanomedicine; Cell Line, Tumor; Animals; Humans; Umbelliferone β-D-galactopyranoside nanoparticles; Diethylnitrosamine; Lactic Acid; Umbelliferones; Particle Size; Rats, Wistar; Original Research; Drug Carriers; 0303 health sciences; Liver Neoplasms; Galactosides; oxidative stress.; Antineoplastic Agents, Phytogenic; diethyl nitrosamine; cytokines; 3. Good health; Nanoparticles; Polyglycolic Acid

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.