Different liposomal formulations of 5-Fluorouracil result in variations to gastrointestinal toxicities

5-Fluorouracil (5FU) treatment can induce severe mucositis, gastrointestinal toxicity. New formulations of 5-FU increase cancer cytotoxicity, such as neutral liposomes (NL), cationic liposomes (CL), and polyethylenimine copper (PEI-Cu) complexes. However, gastrointestinal toxicity for these new formulations remains unclear. We aim to determine if new formulations in 5FU reduce mucositis by reducing intestinal goblet cell and nerve integrity. Sprague Dawley rats were randomly assigned to groups: saline (n=6), 5FU (n=6 ), NL-5FU (n=5), CL-5FU (n=5), PEI-CU-5FU (n=6), NL-PEI-Cu-5FU (n=5) CL-PEI-Cu-5FU (n=5) (Formulations were equivalent to 10mg/kg 5FU in saline). Treatment was administered daily for 5 days. Rats where humanely killed 2 days after treatment. Haematoxylin and Eosin staining for histological change, Alcian Blue-PAS staining for mucin composition, and immunohistochemistry with S100 antibody for nerve integrity were performed. Statistical analysis using Kruskal-Wallis test with Dunns post-test and Mann Whitney U test d were performed. Effect size was determined using Cohens D test. In the jejunum, inflammatory infiltrate increased in PEI-Cu-5FU rats compared to 5-FU controls (p=0.0011). S100 positive nerve bundles increased in NL-5FU rats compared to saline control (p<0.05). S100 positive cells increased in CL-PEI-Cu-5FU rats compared to saline controls. PEI-Cu-5FU formulation was associated with increased inflammatory infiltrate potentially in response to damage in the jejunum. However, liposomal formulations increased S100 positive neural cells, which may offer protection through increased gastrointestinal motility and contraction. While these formulations of 5FU increase cancer cytotoxicity, the gastrointestinal toxicity remains similar. However, further close monitoring of 5FU formulations for gastrointestinal toxicity is warranted.