VCAM-1-targeted methotrexate improved inflammatory-site targeting and anti-inflammatory effects in models.
Evidence
This formulation and preclinical evaluation characterized MTX@LNP-PVCAM-1 nanoparticles, tested HUVEC biocompatibility and synovial fibroblast uptake, growth, migration, and cytokines, and evaluated distribution, efficacy, and safety in AIA rats.
Caveat
The findings come from cell assays and adjuvant-induced arthritis rats, with no human rheumatoid arthritis outcomes and an abstract containing unclear repeated text near the results.
Simplified
OBJECTIVE: Methotrexate (MTX) is widely used for (RA) but has poor targeting and significant side effects. This study developed MTX-loaded 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 (<0.05) and more effectively inhibited the growth (<0.05), migration (<0.05), and secretion of inflammatory cytokines (significantly reduced levels of IL-1β and IL-6,<0.05) of synovial fibroblasts. In animal experiments, the accumulation of MTX@LNP-PVCAM-1 in inflamed sites was significantly higher than that of MTX@LNP (<0.05), demonstrating good targeting. Moreover, it enhanced the anti-inflammatory effects of methotrexate in AIA rats, significantly reducing paw swelling (<0.05) and joint clinical scores (<0.05). Importantly, it had no significant effect on the blood routine indicators of rats (>0.05), indicating no obvious toxicity. p p p p p p p p
CONCLUSION: MTX@LNP-PVCAM-1 combines passive and active targeting, delivering MTX efficiently to inflamed sites and reducing toxicity. This approach enhances anti-inflammatory effects in AIA rats, offering a potential strategy for low-toxicity RA treatment.
Key numbers
37.2%
Increase in Cellular Uptake Efficiency
Compared to unmodified .
1.5×
Decrease in Paw Swelling
Compared to control group in AIA rats.
1.5×
Decrease in Joint Clinical Scores
Compared to control group in AIA rats.
Full Text
We can’t show the full text here under this license.
