EGF-functionalized lipid-polymer hybrid nanoparticles of 5-fluorouracil and sulforaphane with enhanced bioavailability and anticancer activity against colon carcinoma

Biotechnol Appl Biochem. 2022 Oct;69(5):2205-2221. doi: 10.1002/bab.2279. Epub 2021 Nov 25.

Abstract

The present research work describes development of dual drug-loaded lipid-polymer hybrid nanoparticles (LPHNPs) of anticancer therapeutics for the management of colon cancer. The epidermal growth factor (EGF)-functionalized LPHNPs coloaded with 5-fluorouracil (FU) and sulforaphane (SFN) were prepared by one-step nanoprecipitation method. Box-Behnken design was applied for optimizing the material attributes and process parameters. The optimized LPHNPs revealed particle size 198 nm, polydispersity index 0.3, zeta potential -25.3 mV, and drug loading efficiency 19-20.3% for 5-FU and SFN, respectively. EGF functionalization on LPHNPs was confirmed from positive magnitude of zeta potential to 21.3 mV as compared with the plain LPHNPs. In vitro drug release performance indicated sustained and non-Fickian mechanism release nature of the drugs from LPHNPs. Anticancer activity evaluation in HCT-15 colon cancer cells showed significant reduction (p < 0.001) in the cell growth and cytotoxicity of the investigated drugs from various treatments in the order: EGF-functionalized LPHNPs > plain LPHNPs > free drug suspensions. Overall, the research work corroborated improved treatment efficacy of EGF-functionalized LPHNPs for delivering chemotherapeutic agents for the management of colon carcinoma.

Keywords: active targeting; colon cancer; drug delivery; hybrid nanoparticles; quality by design.

MeSH terms

  • Biological Availability
  • Carcinoma*
  • Cell Survival
  • Colonic Neoplasms* / drug therapy
  • Drug Carriers
  • Drug Delivery Systems / methods
  • Epidermal Growth Factor
  • Fluorouracil / pharmacology
  • Humans
  • Lipids
  • Nanoparticles*
  • Particle Size
  • Polymers

Substances

  • Polymers
  • Fluorouracil
  • sulforaphane
  • Epidermal Growth Factor
  • Lipids
  • Drug Carriers