Enhanced anti-angiogenic effects of aprepitant-loaded nanoparticles in human umbilical vein endothelial cells

• Published in: Scientific reports Vol. 14; no. 1; pp. 19837 - 17
• Main Authors: Kaya-Tilki, Elif, Öztürk, Ahmet Alper, Engür-Öztürk, Selin, Dikmen, Miriş
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.08.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67/1059/153; 692/4028/67/2328; Angiogenesis; Angiogenesis Inhibitors - chemistry; Angiogenesis Inhibitors - pharmacology; Anti-angiogenesis; Antiangiogenic agents; Antineoplastic drugs; Aprepitant; Aprepitant - pharmacology; Cancer therapies; Cell migration; Cell Movement - drug effects; Cell Survival - drug effects; Cell viability; Chemotherapy; Cytotoxicity; Drug Carriers - chemistry; Drug delivery; Drug delivery systems; Endothelial cells; Fluorescence microscopy; Gene expression; Human Umbilical Vein Endothelial Cells - drug effects; Humanities and Social Sciences; Humans; HUVEC; Internalization; M2c; multidisciplinary; Nanoparticles; Nanoparticles - chemistry; Particle Size; Polylactic Acid-Polyglycolic Acid Copolymer - chemistry; Polylactide-co-glycolide; Science; Science (multidisciplinary); THP-1; Umbilical vein; Vascular Endothelial Growth Factor A - metabolism; Vascular endothelial growth factor receptors; Aprepitant; THP-1; HUVEC; Anti-angiogenesis; M2c
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-70791-y

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.