Development of 5-fluorouracil/etoposide co-loaded electrospun nanofibrous scaffold for localized anti-melanoma therapy

J Appl Biomater Funct Mater. 2024 Jan-Dec:22:22808000241284439. doi: 10.1177/22808000241284439.

Abstract

Nanofibrous scaffolds have emerged as promising candidates for localized drug delivery systems in the treatment of cutaneous cancers. In this study, we prepared an electrospun nanofibrous scaffold incorporating 5-fluorouracil (5-FU) and etoposide (ETP) for chemotherapy targeting melanoma cutaneous cancer. The scaffold was composed of polyvinyl alcohol (PVA) and chitosan (CS), prepared via the electrospinning process and loaded with the chemotherapeutic agents. We conducted relevant physicochemical characterizations, assessed cytotoxicity, and evaluated apoptosis against melanoma A375 cells. The prepared 5-FU/ETP co-loaded PVA/CS scaffold exhibited nanofibers (NFs) with an average diameter of 321 ± 61 nm, defect-free and homogenous morphology. FTIR spectroscopy confirmed successful incorporation of chemotherapeutics into the scaffold. Additionally, the scaffold demonstrated a hydrophilic surface, proper mechanical strength, high porosity, and efficient liquid absorption capacity. Notably, sustained and controlled drug release was observed from the nanofibrous scaffold. Furthermore, the scaffold significantly increased cytotoxicity (95%) and apoptosis (74%) in A375 melanoma cells. Consequently, the prepared 5-FU/ETP co-loaded PVA/CS nanofibrous scaffold holds promise as a valuable system for localized eradication of cutaneous melanoma tumors and mitigation of adverse drug reactions associated with chemotherapy.

Keywords: Nanofiber; apoptosis; chemotherapy; cytotoxicity; melanoma.

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Chitosan / chemistry
  • Drug Liberation
  • Etoposide* / administration & dosage
  • Etoposide* / chemistry
  • Etoposide* / pharmacokinetics
  • Etoposide* / pharmacology
  • Fluorouracil* / administration & dosage
  • Fluorouracil* / chemistry
  • Fluorouracil* / pharmacology
  • Humans
  • Melanoma* / drug therapy
  • Melanoma* / pathology
  • Nanofibers* / chemistry
  • Polyvinyl Alcohol* / chemistry
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / pathology
  • Tissue Scaffolds / chemistry

Substances

  • Fluorouracil
  • Etoposide
  • Polyvinyl Alcohol
  • Chitosan
  • Antineoplastic Agents