Abstract
Localized and sustained drug delivery offers a promising approach to overcome systemic toxicity and short drug exposure associated with conventional colorectal cancer therapies. In this study, we developed electrospun poly(lactic-co-glycolic acid) (PLGA) fibrous scaffolds incorporating 5-fluorouracil (5-FU) for biodegradable, site-specific chemotherapy. Scaffolds containing 0%, 2.4%, 6%, and 10% (w/w) 5-FU were fabricated and characterized by scanning electron microscopy, showing uniform fibers with dose-dependent changes in diameter and surface texture. In vitro release studies revealed biphasic kinetics, characterized by an initial burst followed by sustained release over 35 days, thereby ensuring prolonged drug availability. Functional assays confirmed selective cytotoxicity against SW620 colorectal cancer cells. In an orthotopic tumor recurrence model, 5-FU-loaded scaffolds, particularly at higher doses, markedly suppressed tumor growth and reduced recurrence. Histological analysis showed disrupted tumor structure, decreased proliferation (Ki-67), reduced angiogenesis (CD31), and diminished extracellular matrix remodeling (fibronectin). Body weight remained stable, indicating minimal systemic toxicity. Together, these findings demonstrate that 5-FU-loaded PLGA scaffolds provide localized, long-term tumor suppression with high spatial precision and low systemic burden, highlighting their potential for post-surgical colorectal cancer therapy.