Novel fabrication of hydroxypropyl-β-cyclodextrin functionalized zein protein nanoparticles Co-encapsulated with bio-molecules to attenuate pregnancy-induced hypertension by inducing trophoblast cells proliferation with TLR4 signaling pathway

Trophoblast dysfunction during pregnancy time is majorly involved to lead pathogenesis of preeclampsia. In the present investigation, the facile nanoformulation by Zein protein particles functionalized with hydroxypropyl-beta-cyclodextrin (β-CD) and co-encapsulated with curcumin and eugenol compounds (Cu/Eu@H-β-CD-ZNPs) is developed to achieve enhanced therapeutic potential in the treatment of preeclampsia. To investigate the positive trophoblast function, trophoblast cells were treated and observed for in vitro cell proliferation, invasion and migration ability under hypoxic condition. The Cu/Eu@H-β-CD-ZNPs have significantly induced the restoration ability of trophoblast cells. In vivo animal study was performed using pregnancy rat models by inducing LPS and observed the hypertension-related factors. The Cu/Eu@H-β-CD-ZNPs prominently down-regulated the expressions of serum and placental pro-inflammatory factors (IL-6, TNF-α, IL1β, and IFN-γ). Additionally, p65 and TLR4 protein expressions in LPS-induced model were effectively downregulated after administration of Cu/Eu@H-β-CD-ZNPs. Results of current investigation provides evidence for combination of Cur/Eug with novel H-β-CD-ZNPs formulation have therapeutic potential on the treatment of pregnancy-induced hypertension by rat models.