Paricalcitol

Paricalcitol is a synthetic vitamin D analogue with a high selectivity for binding to the vitamin D receptor. The mechanism of action involves activation of the vitamin D receptor, which then heterodimerizes with the retinoid X receptor. This VDR-RXR complex translocates to the nucleus and binds to vitamin D response elements on target genes, regulating their transcription. Unlike calcitriol, paricalcitol is a selective vitamin D receptor activator that upregulates VDR in the parathyroid glands without increasing VDR in the intestine and is less active on bone resorption.
Paricalcitol also upregulates the calcium sensing receptor in the parathyroid glands. As a result, paricalcitol reduces parathyroid hormone levels by inhibiting parathyroid proliferation and decreasing PTH synthesis and secretion, with minimal impact on calcium and phosphorus levels. Beyond its classical action on PTH and calcium-phosphorus metabolism, paricalcitol provides additional benefits including reduction of urinary protein, reduction of inflammation, reduction of vascular calcification, renal fibrosis suppression, and anti-tumor effects.

Fig. 1 Pharmacological mechanism of Paricalcitol. (Qu Y.; et al. 2021)

Paricalcitol was efficiently loaded into poly lactic-co-glycolic acid nanoparticles to form PLGA@paricalcitol nanodrugs for the treatment of sepsis-associated acute kidney injury. The PLGA@pari NPs exhibited significant renal accumulation and a markedly prolonged half-life in vivo. The nanodrug demonstrated anti-inflammatory, reactive oxygen species-scavenging and anti-apoptotic effects, effectively ameliorating SA-AKI in septic mouse models. Endotoxins can reduce megalin expression and weaken the renal protective efficacy of paricalcitol. The PLGA nanosystem bypasses this limitation by enhancing paricalcitol enrichment in the kidney through passive targeting.

Fig. 2 Schematic preparation of PLGA@pari NPs and the strategy for SA-AKI treatment. (Li Z.; et al. 2025)