# Alendronic acid modified PLGA drug delivery system loaded with 17β-Estradiol and vitamin D3 has anti-osteoporotic effect

## TL;DR

A new drug delivery system targets bones to treat osteoporosis safely, avoiding side effects of traditional hormone therapy.

## Contribution

A bone-targeted PLGA nanocarrier modified with alendronic acid co-delivers estradiol and vitamin D3 for safer osteoporosis treatment.

## Key findings

- The nanocarrier significantly improved bone mineral density in ovariectomized mice.
- It reduced endometrial thickening caused by estradiol and showed sustained drug release.
- The combination enhanced osteogenesis via activation of the PI3K/AKT/mTOR signaling pathway.

## Abstract

Postmenopausal osteoporosis caused by estrogen deficiency often requires hormone replacement therapy (HRT), but its systemic side effects limit clinical application. Here, we developed a bone-targeted Poly (lactic-co-glycolic acid) (PLGA) nanocarrier modified with Alendronic acid (ADA) to co-deliver 17β-Estradiol (E2) and Vitamin D3 (VitD3), aiming to enhance efficacy and safety. The ADA-functionalized nanoparticles (E2+VD@PLGAIR780ADA) showed high drug loading (7.2 wt% for E2 and 2.3 wt% for VitD3), sustained release (>90 % over 48 h). In ovariectomized (OVX) mice, targeted delivery significantly improved bone mineral density, restored trabecular structure, and reduced serum bone resorption markers, while markedly alleviating E2-induced endometrial thickening. In vivo imaging confirmed selective bone accumulation. Mechanistically, co-administration of VitD3 and E2 elicits enhanced pro-osteogenic effects by virtue of VitD3-mediated Vitamin D Receptor (VDR) upregulation and amplified E2-induced estrogen receptor (ER) expression, which collectively drive robust activation of the PI3K/AKT/mTOR signaling cascade.This bone-specific nanoplatform offers a promising and safer strategy for osteoporosis therapy beyond conventional HRT.

E2+VD@PLGAIR780ADA targets bones to improve osteogenesis.Image 1

E2+VD@PLGAIR780ADA targets bones to improve osteogenesis.