Background: Tamoxifen (TMX) has been in clinical use for over 40 years and can be considered
the standard for breast cancer chemoprevention in high-risk patients. Unfortunately, patient
compliance to treatment is low due to systemic toxicity.
Objective: The present study demonstrates the use of a nanochannel Delivery System (nDS) for controlled
and sustained local release of TMX in mammary tissue.
Method: TMX release in vitro from the nDS was assessed using two different concentrations of the
solubilizer PEG400. The optimal configuration was then studied in 9-week old NMU-treated Sprague
Dawley rats, and the release profile of TMX analyzed with LC-MS/MS. Systemic and organ toxicity
Results: Although highly water insoluble, we showed that through utilization of PEG400, we were able
to sustain the release of TMX in vitro for 2 months. In vivo, we released TMX from nDS implants and
reached relevant plasma concentrations (>50 ng/ml). Our study showed sustained low dose delivery of
TMX over several months from the implant placed adjacent to the mammary gland, thereby minimizing
whole-body exposure and associated side effects. Compared to the oral TMX treated group, the nDSTMX
group maintained higher body weight and showed lower uterine weight. Compared to the sham
group, TMX treatment reduced the number of mammary gland aggregates without affecting liver
Conclusion: We demonstrate that the nDS is a valid technology for long-term delivery of TMX. Additional
tests are required to prove if the nDS is applicable for breast cancer prevention to offer an avenue
to reduce the incidence of estrogen sensitive breast cancer.