Enhanced anti-angiogenic effects of aprepitant-loaded nanoparticles in human umbilical vein endothelial cells
Elif Kaya Tilki, A. Alper Öztürk, Selin Engür, Miriş Dikmen
Abstract
Recent advancements in cancer therapy have led to the development of novel nanoparticle-based drug delivery systems aimed at enhancing the efficacy of chemotherapeutic agents. This study focuses on evaluating aprepitant-loaded PLGA and Eudragit RS 100 nanoparticles for their potential antiangiogenic effects. Characterization studies revealed that aprepitant-loaded nanoparticles exhibited particle sizes ranging from 208.50 to 238.67 nm, with monodisperse distributions (PDI < 0.7) and stable zeta potentials (between − 5.0 and − 15.0 mV). Encapsulation efficiencies exceeding 99% were achieved, highlighting the efficacy of PLGA and Eudragit RS 100 as carriers for aprepitant. Cellular uptake studies demonstrated enhanced internalization of aprepitant-loaded nanoparticles by HUVEC cells compared to free aprepitant, as confirmed by fluorescence microscopy. Furthermore, cytotoxicity assays revealed significant dose-dependent effects of aprepitant-loaded nanoparticles on HUVEC cell viability, with IC 50 values at 24 h of 11.9 µg/mL for Eudragit RS 100 and 94.3 µg/mL for PLGA formulations. Importantly, these nanoparticles effectively inhibited HUVEC cell migration and invasion induced by M2c supernatant, as evidenced by real-time cell analysis and gene expression studies. Moreover, aprepitant-loaded nanoparticles downregulated VEGFA and VEGFB gene expressions and reduced VEGFR-2 protein levels in HUVEC cells, highlighting their potential as antiangiogenic agents. Overall, this research underscores the promise of nanoparticle-based aprepitant formulations in targeted cancer therapy, offering enhanced therapeutic outcomes through improved drug delivery and efficacy against angiogenesis.