Multiple lines of evidence support a role for
curcumin in
cancer chemoprevention. Nonetheless, despite its reported efficacy and safety profile, clinical translation of
curcumin has been hampered by low oral bioavailability, requiring infeasible 'mega' doses for achieving detectable tissue levels. We have engineered a polymeric nanoparticle encapsulated formulation of
curcumin (NanoCurc) to harness its full therapeutic potential. In the current study, we assessed the
chemoprevention efficacy of NanoCurc administered via direct intraductal (i.duc) injection in a chemical
carcinogen-induced rodent
mammary cancer model. Specifically, Sprague-Dawley rats exposed to systemic
N-methyl-N-nitrosourea were randomized to receive either oral free
curcumin at a previously reported 'mega' dose (200mg/kg) or by direct i.duc injection of free
curcumin or NanoCurc, respectively, each delivering 168 µg equivalent of
curcumin per rodent teat (a ~20-fold lower dose per animal compared to
oral administration). All three
chemoprevention modalities resulted in significantly lower mammary
tumor incidence compared with control rats; however, there was no significant difference in
cancer incidence between the oral dosing and either i.duc arms. On the other hand, mean
tumor size, was significantly smaller in the i.duc NanoCurc cohort compared with i.duc free
curcumin (P < 0.0001), suggesting the possibility of better resectability for 'breakthrough'
cancers. Reduction in
cancer incidence was associated with significant decrease in nuclear factor -κB activation in the NanoCurc treated mammary epithelium explants, compared to either control or oral
curcumin-administered rats. Our studies confirm the potential for i.duc NanoCurc as an alternative to the oral route for
breast cancer chemoprevention in high-risk cohorts.