In vivo performance of 5-fluorouracil encapsulated on bacterial nanocellulose in an azoxymethane-dextran sulphate sodium induced colorectal cancer: Drug release profiles, histological and biomarkers analysis

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, largely due to its chronic progression and frequent diagnosis at advanced stages. Although surgical resection remains the gold standard for CRC treatment, adjuvant chemotherapy with 5-fluorouracil (5FU) is commonly required; however, its clinical effectiveness is limited by systemic toxicity and severe side effects. In this study, we evaluated the in vivo performance of a bacterial nanocellulose (BNC)-based 5FU encapsulation system in a murine CRC model induced by azoxymethane/dextran sulfate sodium (AOM/DSS). Drug release behavior was analyzed under colonic conditions, and treatment efficacy was assessed through tumor progression and the expression of biomarkers associated with apoptosis and cell proliferation, comparing free and encapsulated 5FU. 5FU release from BNC capsules was predominantly diffusion-controlled and exhibited a delayed onset at colonic pH (pH 5), attributed to molecular interactions between 5FU and the BNC matrix, supporting the suitability of BNC as a colon-targeted drug delivery platform. Both free and encapsulated 5FU treatments significantly delayed malignancy progression; however, tumor advancement accelerated after treatment discontinuation, confirming the therapeutic activity of both formulations. Biomarker analysis revealed activation of apoptotic pathways at week 8 in both groups, while encapsulated 5FU induced a marked downregulation of JNK, STAT3, and p70S6K signaling proteins involved in cancer cell proliferation. Overall, these findings demonstrate that BNC-based encapsulation enhances the bioavailability and therapeutic performance of 5FU in an AOM/DSS-induced CRC model, highlighting its potential as a bioorganic and safer strategy for colorectal cancer therapy. Further optimization of pharmaceutical formulations will support progression toward clinical evaluation.