Codelivery of methotrexate and silibinin by niosome nanoparticles for enhanced chemotherapy of CT26 colon cancer cells

Biomed Mater. 2024 Jul 12;19(5). doi: 10.1088/1748-605X/ad5d9b.

Abstract

Colon cancer (CC) is one of the most prevalent cancers in the world, and chemotherapy is widely applied to combat it. However, chemotherapy drugs have severe side effects and emergence of multi drug resistance (MDR) is common. This bottleneck can be overcome by niosome nanocarriers that minimize drug dose/toxicity meanwhile allow co-loading of incompatible drugs for combination therapy. In this research, silibinin (Sil) as a hydrophobic drug was loaded into the lipophilic part, and methotrexate (MTX) into the hydrophilic part of niosome by the thin film hydration (TFH) method to form Nio@MS NPs for CT26 colon cancer therapyin vitro. Our results indicated synthesis of ideal niosome nanoparticles (NPs) with spherical morphology, size of ∼100 nm, and a zeta potential of -10 mV. The IC50value for Nio@MS was determined ∼2.6 µg ml-1, which was significantly lower than MTX-Sil (∼6.86 µg ml-1), Sil (18.46 µg ml-1), and MTX (9.8 µg ml-1). Further, Nio@MS significantly reduced cell adhesion density, promoted apoptosis and increased gene expression level of caspase 3 and BAX while promoted significant downregulation of BCL2. In conclusion, the design and application of niosome to co-administer Sil and MTX can increase the drugs cytotoxicity, reduce their dose and improve anti-cancer potential by combating MDR.

Keywords: codelivery; colon carcinoma; methotrexate; niosome; silibinin.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis* / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colonic Neoplasms* / drug therapy
  • Colonic Neoplasms* / metabolism
  • Colonic Neoplasms* / pathology
  • Drug Carriers / chemistry
  • Humans
  • Liposomes / chemistry
  • Methotrexate* / chemistry
  • Methotrexate* / pharmacology
  • Mice
  • Nanoparticles / chemistry
  • Nickel / chemistry
  • Silybin* / chemistry
  • Silybin* / pharmacology

Substances

  • Methotrexate
  • Silybin
  • Nickel
  • Liposomes
  • nickel monoxide
  • Antineoplastic Agents
  • Drug Carriers