Formulation and Evaluation of VCAM-1-Targeted Methotrexate Lipid Nanoparticles for Rheumatoid Arthritis Therapy

作者：Ren Na, Jianmei Jing, Hua Yang, Li Ye, Xiaofeng Yuan, Xuegang Sun, Jiangfan Han, Jiajun Wang, Zhenhua Tong, Guangbin He, Weiliang Ye · 发表于：International Journal of Nanomedicine · 年份：2025 · DOI：10.2147/ijn.s532163 · 被引用次数：6 · 研究领域：Rheumatoid Arthritis Research and Therapies、Advancements in Transdermal Drug Delivery、Advanced Drug Delivery Systems

Objective: Methotrexate (MTX) is widely used for rheumatoid arthritis (RA) but has poor targeting and significant side effects. This study developed MTX-loaded lipid nanoparticles modified with PVCAM-1 peptide (MTX@LNP-PVCAM-1) to enhance targeting and reduce toxicity. Methods: MTX@LNP-PVCAM-1 was prepared using the thin-film dispersion method. Particle size and morphology were assessed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Biocompatibility was tested using human umbilical vein endothelial cells (HUVEC) and hemolysis assays. Cellular uptake was examined via fluorescence microscopy, while cytotoxicity and cell migration inhibition were evaluated using CCK-8 and scratch assays. Inflammatory cytokines (IL-1β, IL-6) were measured by ELISA. Distribution in adjuvant-induced arthritis (AIA) rats was observed using in vivo imaging, and safety and anti-inflammatory effects were assessed through blood tests, paw volume, joint scores, and histology. Results: MTX@LNP-PVCAM-1 had an average particle size of 168.5 nm, PDI of 0.142, and zeta potential of − 12.1 mV, with spherical morphology. It exhibited pH responsiveness and good biocompatibility. Compared with unmodified MTX@LNP, PVCAM-1 surface modification significantly increased cellular uptake efficiency ( p < 0.05) and more effectively inhibited the growth ( p < 0.05), migration ( p < 0.05), and secretion of inflammatory cytokines (significantly reduced levels of IL-1β and IL-6, p < 0.05) of sy...