Design, Development and Optimization of 5-Fluorouracil Nanohydrogel for Improved Anticancer Therapy.

Autor: Dange, Yuvraj, Salunkhe, Vijay, Honmane, Sandip, Thorawade, Koustubh
Zdroj: BioNanoScience; Jun2024, Vol. 14 Issue 2, p1696-1714, 19p
Abstrakt: The primary objective of this study was to develop a nanohydrogel formulation of 5-fluorouracil (5-FU) for treating skin cancer that could reduce the dosing frequency and dose-related toxicity and improve its bioavailability at the site of action. Chitosan (CS)-complexed 5-FU nanoparticles (5-FCNPs) were prepared using the ionic gelation technique, which offers advantages such as simplicity, absence of organic solvents, and non-toxicity. The optimization was done using a 32 factorial design approach. The concentrations of CS and stirring speed were considered independent variables while effect on various dependent parameters such as particle size, zeta potential, and % entrapment efficiency was investigated for the development of 5-FCNPs. In contrast, the concentration of carbopol and triethanolamine is considered independent variables while viscosity, % drug release, and skin permeation were investigated as dependent parameters for the optimization of nanohydrogel formulation. The developed nanohydrogel underwent a comprehensive characterization process involving infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), pH assessment, morphological analysis, spreadability, consistency, and in vitro cytotoxicity. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) techniques were applied to assess the even distribution of nanoparticles within the hydrogel matrix. Optimized nanohydrogel formulation (5-FNH9) showed 79.9%, 85.78%, and 3.188% of % entrapment efficiency, % drug release, and skin permeation, respectively. The percentage of drug release from the 5-FNH9 was 34.62 ± 0.51% over 12 h followed by the zero-order kinetic release mechanism. The IC50 of the 5-FU solution was greater than the 5-FNH9 formulation. The formulated 5-FU nanohydrogel exhibited pH-responsive controlled drug release and improved skin permeation, and this could be used promisingly for the delivery of 5-FU in the treatment of skin cancer. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index