Application of Nanocarrier-Based Targeted Drug Delivery in the Treatment of Liver Fibrosis and Vascular Diseases
DOI:
https://doi.org/10.71222/bc9c9s73Keywords:
targeted drug delivery, PLGA nanocarriers, liver fibrosis, vascular inflammation, ligand modification, cellular uptake, anti-fibrotic therapyAbstract
Liver fibrosis and vascular diseases are often accompanied by chronic inflammation and excessive extracellular matrix deposition, posing significant clinical challenges. In this study, we developed a poly (lactic-co-glycolic acid) (PLGA)-based nanocarrier system for targeted delivery of anti-inflammatory and antifibrotic agents. The nanocarriers were fabricated via a nanoprecipitation method and functionalized with α-smooth muscle actin (α-SMA) antibodies and vascular cell adhesion molecule-1 (VCAM-1) aptamers to enhance cell-specific targeting. Characterization revealed uniform spherical morphology with a mean particle size of 150 ± 20 nm, increasing to 165 ± 25 nm after ligand modification, and a stable zeta potential of -20 ± 5 mV. Flow cytometry confirmed a conjugation efficiency of 85 ± 5%. Confocal imaging showed 2.3-fold and 2.5-fold increases in uptake by hepatic stellate and vascular endothelial cells, respectively. ELISA results demonstrated significant reductions in TNF-α, IL-6, Collagen I, and Fibronectin levels following treatment with drug-loaded nanocarriers. In vivo studies using C57BL/6 mouse models of liver fibrosis and vascular injury confirmed improved therapeutic efficacy. The nanocarrier group showed marked reductions in ALT (60 ± 6 U/L), AST (80 ± 8 U/L), liver fibrosis area (15 ± 3%), and atherosclerotic plaque (12 ± 2%) compared to controls. No significant adverse effects were observed. These results suggest that ligand-modified PLGA nanocarriers provide a promising strategy for targeted therapy of fibrosis-related diseases improved efficacy and safety profiles.
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