Fabrication and Optimization of Electrospun Polymeric Nanofibers Loaded with 5-Fluorouracil and Rosemary Extract

Abstract

Background: Topical 5-fluorouracil (5FU) is one of the most prescribed medications for different types of skin cancer; however, it is associated with drug resistance and adverse effects. Rosemary extract has promising dose-dependent antitumor effects, as well as a synergistic effect in combination with 5-fluorouracil, besides sensitization of the 5-FU-resistant cells. Objective: Polymeric nanofibers loaded with 5FU and rosemary extract were optimized to combine both ingredients in one controlled release drug delivery system, aiming to enhance the efficacy while retaining the adverse effects. Method: Polymeric nanofibers loaded with 5-FU and rosemary were fabricated via electrospinning technique. Design expert software was utilized to study the effect of independent variables, including polymer concentration, voltage, and feeding rate on the characteristics of the resulting nanofibers. Afterwards, the FTIR spectrum and release kinetic of the drug and extract from the optimized nanofibers and their cytotoxic effect against A375 cell line were investigated. Results: The formulation composed of 6.65% PVA electrospun at 1 mL.h-1 and 17.5kV was chosen as the optimum fabrication condition. The mean diameter of the optimized nanofibers was 755 nm. The drug and rosemary extract contents were 75.38 and 93.42%, respectively. The fabrication yield was 100%, bioadhesion force was 1.28 N, and bead abundance was 10 per field. The cytotoxicity of the optimized formulation was significantly higher than the control groups. Conclusion: According to the appropriate loading percentage, release efficiency and release kinetics, bioadhesion force, and cytotoxicity, these nanofibers could be further investigated as a topical treatment option to increase the efficacy of 5-FU.