PD-E2: a nano-scaled delivery for estradiol to decrease uterus damage and increase bone mineral density

Qiqi Feng, Hao Gong, Haimei Zhu, Xiaoyi Zhang, Yaonan Wang, Yifan Yang, Jianhui Wu, Ming Zhao, Shiqi Peng
In: Journal of Materials Chemistry B · 2025 · vol. 13(23) , pp. 6679–6688 · doi:10.1039/d4tb02764g · PMID:40365736 · W4409992926
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Abstract

PD-E2 was capable of simultaneously blocking bone loss and downregulating the expression of ALP in the serum, which made serum ALP a potential biomarker for monitoring the bone health of menopause women clinically.
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PD-E2: a nano-scaled delivery for estradiol to decrease uterus damage and increase bone mineral density† Abstract It is well known that a specific application of 17β-estradiol (E2) is in hormone replacement therapy (HRT), but it is capable of inducing uterine gland cysts. However, the concentration of E2 that causes uterine gland cysts and bone loss remains unknown. To better understand this, we used an ovariectomized (OVX) mouse as the animal model and administered poly-α,β-DL-aspartyl-Lys-coupled E2 (PD-E2) as the bone targeting agent. HPLC-FT-MS analysis showed that the amounts of E2 in the uterus and the femurs of the OVX mice treated with 2.3 μmol kg−1 per day of E2 were 0.62 ± 0.15 ng g−1 and 0.31 ± 0.09 ng g−1, respectively, while the amounts of E2 in the uterus and the femurs of the OVX mice treated with 10 nmol kg−1 per day of PD-E2 were 0 ± 0 ng g−1 and 1.11 ± 0.27 ng g−1, respectively. The data suggested that if the amount of E2 in the uterus was equal to 0.62 ± 0.15 ng g−1, the uterine gland will form cysts, and if the amount of E2 in the femurs was less than 0.31 ± 0.09 ng g−1, the bone loss will be significant. Furthermore, the nano-scaled PD-E2 agent reported in this study provides an innovative strategy for HRT.

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