Nanoparticles-loaded nanofiber topical patch of 5-fluorouracil: fabrication, characterization, and preclinical assessment in skin cancer

Skin cancer is the uncontrolled proliferation of abnormal skin cells. It is mostly caused by unrepaired deoxyribonucleic acid (DNA) damage to skin cells, which results in mutations, or genetic flaws, that cause skin cells to reproduce rapidly and develop malignant tumors. This study aimed to develop and analyze nanoparticle-loaded multilayered nanofibers (M-NFs) for the treatment of skin cancer. 5-Fluorouracil (5-FU) was chosen as the chemotherapy medication. Poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles were created utilizing a double emulsion technique. The 2^5-2 fractional factorial design was used to test a variety of process and formulation parameters. The resultant nanoparticles were assessed for zeta potential, entrapment efficiency, particle size, shape. The optimized drug-loaded PLGA nanoparticle had a particle size of 178.4 ± 6.1 nm, a zeta potential of -28.2 mV, and an entrapment efficiency of 86.12% ± 2.1%. Transmission electron microscopy images showed uniformly sized spherical particles. Additional drug-loaded PLGA nanoparticles were integrated into M-NFs. The produced nanofibers were thoroughly characterized, and comparative <i>in-vitro</i> drug diffusion tests were conducted. <i>In-vitro</i> drug diffusion studies of drug-loaded PLGA nanoparticles into M-NFs demonstrated regulated release for up to 7 d. Further <i>in-vivo</i> effectiveness, histopathology, and immunohistochemistry studies were performed on SCID mice. According to the findings, the growth of skin cancer tumors has been steadily reduced, indicating that there are effective treatments for skin cancer. Developed multilayered electrospun nanofiber system demonstrates superior sustained release, enhanced drug localization, and improved cytotoxic efficacy compared to conventional nanofiber-only or nanoparticle-only formulations. This addition effectively underscores the novelty and therapeutic advantage of our integrated delivery platform.