Nanotamoxifen Delivery System: Toxicity Assessment After Oral Administration and Biodistribution Study After Intravenous Delivery of Radiolabeled Nanotamoxifen

Tamoxifen is the most prescribed anticancer oral drug for increasing overall survival and decreasing recurrence and the risk of contralateral disease. However, some side effects, such as endometrial and liver tumors, thromboembolic disorders, and drug resistance, are associated with long-term tamoxifen treatment. We assessed the hematologic and organ toxicity after oral administration of three different doses of nanotamoxifen formulations. We also performed biodistribution studies of Technetium-99m ((99m)Tc)-nanotamoxifen after intravenous administration. The results demonstrated that nanotamoxifen was well-tolerated, with no adverse effect on biochemical parameters of blood and at the cellular level. Nitric oxide (NO) levels indicated no free radical formation. Oral nanotamoxifen is well-tolerated, with no hepatic or renal toxicity. Intravenous nanotamoxifen has potential to escape the liver, and is known for producing the harmful metabolite 4-hydroxytamoxifen (4OH-tamoxifen), which can cause uterine cancer.