Oral
tamoxifen used in the prevention and treatment of
ductal carcinoma in situ (
DCIS) (
estrogen-positive) patients has limited acceptance, due to its adverse side effects. The efficacy of
tamoxifen is related to its major metabolite,
4-hydroxytamoxifen. Local transdermal
therapy of
4-hydroxytamoxifen to the breast might avert the toxicity of oral
tamoxifen, while maintaining efficacy. We aim to study the skin irritancy, as well as to evaluate the efficacy of the developed transfersome formulations, with/without
emu oil, using a syngeneic mouse model of
breast cancer. We also quantified
tamoxifen/4-
hydroxytamoxifen concentrations in blood plasma and performed histopathology. The skin irritancy test showed that the pure
emu oil and transfersome formulations with or without the
emu oil did not cause skin irritancy in the animals studied. A sensitive and specific LC-MS/MS method for the quantification of
tamoxifen and
4-hydroxytamoxifen was developed and validated. Studies on
tumor volume and
necrosis (histopathology) using the
breast cancer mouse model showed that the
4-OHT transfersomal formulations, with and without
emu oil, showed comparable efficacy with that of orally administered
tamoxifen. However, the transfersomal formulations, with and without
emu oil, resulted in significantly lower (10.24 ± 0.07 and 32.45 ± 0.48 ng/mL, respectively) plasma concentrations of
4-hydroxytamoxifen, compared to the oral
tamoxifen (TAMX) group (634.42 ± 7.54 ng/mL). This study demonstrated the potential use of
emu oil in a local transdermal formulation for the treatment of
breast cancer and its reduced adverse effects.