Investigating the Toxicity and Biodistribution of Boron-loaded Liposomes in Canine and Feline Models.

Abstract

Boron neutron capture therapy (BNCT) is a targeted cancer treatment that relies on the selective accumulation of boron-containing agents in tumor cells, followed by irradiation with low-energy neutrons to produce a cytotoxic reaction. Liposome-mediated delivery systems have shown promise in improving the biodistribution and tumor specificity of boron agents in mice. This study aimed to evaluate the toxicity of boron-loaded liposomes (MAC/TAC formulations) in canine and feline models and to measure biodistribution in dogs with naturally occurring tumors. Boron-loaded liposomes were prepared using a thin-film hydration method and characterized for size, stability, and boron content. Toxicity was assessed by clinical signs, complete blood count (CBC), serum chemistry, and histopathological analysis. Biodistribution was analyzed using inductively coupled plasma optical emission spectroscopy (ICP-OES) to quantify boron levels in blood, tumors, and vital organs. Adverse reactions were observed in both species, with mild nausea and transient fever being the most common. Higher doses resulted in hematological changes, including leukocytosis and thrombocytopenia, particularly in feline subjects. Biodistribution studies showed a tumor-to-blood boron ratio <1:1 in most cases, which is insufficient for effective BNCT. Findings indicated that cancer-bearing dogs receiving boron-containing liposomes experienced significant toxicity responses, including lethargy, nausea, and inflammatory reactions, which were dose- and dose rate-dependent, consistent with the previously described C activation-related pseudoallergy (CARPA) syndrome. The role of this response on boron biodistribution warrants further investigation.