Fabrication of hesperidin nanoparticles loaded by poly lactic co-Glycolic acid for improved therapeutic efficiency and cytotoxicity

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):378-394. doi: 10.1080/21691401.2018.1559175.

Abstract

Hesperidin, as a flavonone, is recognized as promising anti-inflammatory, antioxidant, and anticancer agent. Its poor bioavailability is crucial bottleneck for therapeutic efficacy. To enhance the stability and bioactive potentials, hesperidin -PLGA-Poloxamer 407 was successfully prepared to minimize or overcome problems associated with hesperidin absorption. The characteristics of nanohesperidin were testing by in vitro dissolution study, XRD, FTIR, PSA and SEM. Antioxidant effects of nanohesperidin were studied. The structure-activity relationship analysis with antioxidant pharmacophore has been performed by using density functional theory method and quantum chemical calculations. The structural properties were investigated using Becke three-parameter hybrid exchange and the Lee-Yang-Parr correction functional methods. Nanohesperidin was found to decrease the H2O2 activity-induced DNA instability. Blood compatibility on human erythrocytes was confirmed by haemolytic and in vitro toxicity assessments. The in vitro anticancer activity of nanohesperidin towards MCF-7 cells using various parameters was carried out. The nanohesperidin was found to exert cell growth arrest, activated DNA fragmentation and induced apoptotic cell death through caspase-3 and p53-dependent pathways. These findings showed that nanohesperidin play an important role in its anticancer effects, suggesting might be used for clinical trials and can represent driving formulation for novel chemotherapeutic agents.

Keywords: MCF-7 cells; Modified nanohesperidin; PLGA; antioxidant; blood compatibility; cytotoxicity.

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Caspase 3 / metabolism
  • DNA Damage
  • Drug Carriers / chemistry*
  • Drug Carriers / toxicity
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hemolysis / drug effects
  • Hesperidin / chemistry*
  • Hesperidin / pharmacology*
  • Humans
  • MCF-7 Cells
  • Models, Molecular
  • Molecular Conformation
  • Nanoparticles / chemistry*
  • Particle Size
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Tumor Suppressor Protein p53
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Hesperidin
  • Caspase 3