An investigation on the use of tributyrin nanoemulsions for docetaxel delivery

Tributyrin, an oil with anticancer properties, is a good solubilizer for docetaxel, an agent used in the treatment of several cancers. In this paper, the interaction between tributyrin and docetaxel was investigated in vitro in search of a potential synergistic effect. Then, nanosized emulsions (ca. 100 nm) combining both tributyrin and docetaxel were developed and tested for their cell growth inhibition properties and their systemic toxicity in healthy mice. Tributyrin alone or in combination with docetaxel, and formulated or not in a nanoemulsion, was found to exhibit a modest in vitro antimitotic activity. No synergism could be detected under the conditions tested. Furthermore, no induction of apoptosis was revealed by flow cytometry experiments when treating HL-60 and PC-3 cells with tributyrin. When injected intravenously into mice as a nanoemulsion, the docetaxel/tributyrin combination displayed extreme toxicity. Therefore, the current data preclude its combination with docetaxel in nanoemulsions for intravenous administration.