Cationic Solid Lipid Nanoparticles of Resveratrol for Hepatocellular Carcinoma Treatment: Systematic Optimization, in vitro Characterization and Preclinical Investigation

Int J Nanomedicine. 2020 Nov 23:15:9283-9299. doi: 10.2147/IJN.S277545. eCollection 2020.

Abstract

Aim: The present study focuses on the development and evaluation of the resveratrol (RV)-loaded cationic solid lipid nanoparticles (RV-c-SLNs) for the management of hepatocellular carcinoma (HCC).

Materials and methods: Optimization of formulation was performed using factorial design, and further in vitro drug release, cytotoxicity, biodistribution, in vivo preclinical, and biochemical evaluation were carried out.

Results: The optimized formulation exhibited uniform size, homogeneous disparity, positive zeta potential, and stability over 12-week storage at 25°C/60% RH. The in vitro drug release and cytotoxicity study showed 60% drug release within the first 6 hours and comparatively higher cytotoxicity on HepG2 cell line by resveratrol-solid lipid nanoparticle (RV-SLN) as compared to the RV solution. In addition, an anticancer action and biodistribution study on a rat model of HCC showed significant reduction of tumor volume and higher accumulation in the tumor tissue from RV-c-SLN (P<0.01) over RV solution and RV-SLN. Furthermore, RV-c-SLN showed significant down-regulation in the levels of pro-inflammatory cytokines and balancing of antioxidant enzymes. Histopathological investigation showed reduced occurrence of hepatic nodules, necrosis formation, infiltration of inflammatory cells, blood vessels inflammation, and cell swelling.

Conclusion: Overall, the obtained results construed that RV-c-SLN with improved antitumor activity as clearly evident from in vitro, in vivo, and biochemical investigations.

Keywords: cationic solid lipid; diethyl nitrosamine; hepatocellular carcinoma; inflammatory biomarkers; resveratrol; solid lipid nanoparticles.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Body Weight / drug effects
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Cations
  • Cell Death / drug effects
  • Drug Carriers / chemistry
  • Drug Liberation
  • Inflammation Mediators / metabolism
  • Lipids / chemistry*
  • Liver / drug effects
  • Liver / pathology
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Male
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Organ Size / drug effects
  • Particle Size
  • Rats, Wistar
  • Resveratrol / pharmacology
  • Resveratrol / therapeutic use*
  • Static Electricity
  • Tissue Distribution / drug effects
  • Tumor Burden / drug effects

Substances

  • Antioxidants
  • Cations
  • Drug Carriers
  • Inflammation Mediators
  • Lipids
  • Resveratrol