PD-E2: A nano-scaled delivery for estradiol to decrease uterus damage and increase bone benefit of the hormone replacement therapy

Abstract

It is well known that a specific application of 17β-estradiol (E2) is for hormone replacement therapy (HRT), and E2 is capable of inducing uterine gland cysts. However how much E2 can cause uterine gland cysts and prevent bone loss remain unknown. To clarify the issues, we used ovariectomized (OVX) mouse as the animal model and prepared poly-ɑ,β-dl-aspartyl-Lys coupled E2 (PD-E2) as the bone targeting agent. HPLC-FT-MS analysis showed that the amount of E2 in the uterus and the femurs of the OVX mice treated by 2.3µmol/kg/day of E2 were 0.62±0.15 ng/g and 0.31±0.09 ng/g respectively, while the amount of E2 in the uterus and the femurs of the OVX mice treated by 10 nmol/kg/day of PD-E2 were 0±0 ng/g and 1.11±0.27 ng/g respectively. The data suggested that if the amount of E2 in the uterus was equal to 0.62±0.15 ng/g the uterine gland will cysts, and if the amount of E2 in the femurs was less than 0.31±0.09 ng/g the bone will be lost. Furthermore, the nano-scaled PD-E2 of the present paper provided an innovative strategy for HRT.