Design and Evaluation of PLGA-Based Nanocarriers for Targeted and Sustained Drug Delivery in Vascular Disorders

Abstract

Vascular diseases, including atherosclerosis and vascular inflammation, have high incidence and mortality rates worldwide. Current drug therapies are limited by short circulation time, broad non-specific distribution, insufficient efficacy, and significant side effects. This study aimed to develop and optimize a targeted nanodrug delivery system based on poly(lactic-co-glycolic acid) (PLGA) to improve drug accumulation and therapeutic outcomes at vascular lesion sites. Nanoparticles prepared by the solvent evaporation-self-assembly method had an average diameter of 145.6 {+/-} 12.3 nm, a zeta potential of -21.4 {+/-} 3.7 mV, and showed uniform spherical morphology. The encapsulation efficiency (EE%) was 82.3 {+/-} 4.5%, and the drug loading (DL%) was 9.6 {+/-} 1.1%, indicating good drug-carrying ability. For surface modification, conjugation of ligands to the ends of PEG chains balanced the conflict between "stealth" and "affinity," maintaining circulation stability while restoring effective binding to vascular endothelial cells. Drug release experiments demonstrated a biphasic release profile in PBS (pH 7.4): about 40% was released within 0-12 h, and cumulative release reached 76.5 {+/-} 3.2% at 72 h. Kinetic analysis fitted the Higuchi model (R2 = 0.983), suggesting diffusion as the main driving mechanism. This predictable and controllable release behavior can provide both rapid effect in the acute phase and sustained therapy in the chronic phase. Overall, the PLGA nanocarrier system proposed in this study showed clear advantages in physicochemical properties, surface functionalization, and drug release kinetics. It can achieve prolonged circulation, high targeting efficiency, and controlled release in the treatment of vascular diseases. This work provides experimental evidence to overcome the limitations of conventional drug therapy and lays the foundation for developing multifunctional and clinically translatable nanodrug delivery platforms for personalized treatment.