Abstract
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.
Highlights
Breast cancer (BC) is the most common cancer among women; impacting over two million women each year
In Malaysia, the incidence, mortality, and prevalence of BC was reported to be the highest among other cancers; where 7593 new cases were reported in 2018 [1].Population-based BC screening programs found that ductal carcinoma in situ (DCIS) represents 20–25% of all BC, and from statistical analysis it is predicted that 1 in 33 women are likely to be diagnosed with DCIS of the breast during their lifetime [2]
We report the results from skin irritancy studies, as well as the results of the evaluation efficacy of the transfersome formulations with emu oil, using a syngeneic mouse model of breast cancer [28] and quantification of TAMX/4-OHT concentration in blood plasma and histopathology
Summary
Breast cancer (BC) is the most common cancer among women; impacting over two million women each year. It is considered to be non-invasive because it normally does not spread into any of the normal surrounding breast tissues. Women with DCIS that are estrogen receptor (ER)-positive can be given hormone therapy with tamoxifen (TAMX), which is associated with decreased risk of future breast events, including invasive cancer and DCIS in unaffected breast [5,6,7]. Oral administration of TAMX is proven to be quite effective. It can cause certain side-effects like distaste for food, abdominal cramps, nausea, and vomiting. A few patients experience some in-frequent side-effects, such as endometrial carcinoma, ocular problems, and thromboembolic disorders and acquired drug-resistance on long-term therapy [9,10,11,12]
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