Sustained Delivery of Tamoxifen from a Nanofluidic Delivery Platform

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 was evaluated. 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 weight. 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.