Synthesis, characterization, and nanoparticle formulation and evaluation of rosuvastatin-curcumin conjugate for...

The present study describes the rational design, synthesis, and nano formulation of a Rosuvastatin-Curcumin (RS-CU) conjugate aimed at overcoming the limitations of poor bioavailability and systemic adverse effects associated with conventional statin therapy. The RS-CU conjugate was synthesized via an esterification reaction and confirmed through FTIR, NMR, and mass spectrometry. The conjugate was successfully encapsulated into poly(lactic-co-glycolic acid) (PLGA) nanoparticles, which exhibited uniform spherical morphology with an average particle size of 152.6 ± 3.2 nm, a zeta potential of -22.4 ± 1.1 mV, and an entrapment efficiency of 82.7 ± 2.5%. In vitro release studies indicated sustained, diffusion-controlled drug release over 12 h, following the Higuchi kinetic model (R² = 0.982). Ex vivo intestinal permeation studies revealed significantly higher permeation of RS-CU nanoparticles (82.67 ± 1.38%) compared to the pure conjugate solution (54.25 ± 1.74%) (p < 0.01), demonstrating enhanced absorption potential. Cytotoxicity evaluation on RAW 264.7 macrophages showed markedly improved growth inhibition for RS-CU nanoparticles (IC₅₀ = 23.3 μM) relative to single-drug nano formulations, indicating synergistic therapeutic action. The conjugate also exhibited potent COX-2 inhibition (84.62 ± 1.18% at 200 μg/mL), comparable to diclofenac sodium, supported by molecular docking interactions with key residues (Arg120, Ser530, Tyr355). Overall, the RS-CU conjugate-loaded nanoparticles provide a dual lipid-lowering and anti-inflammatory therapeutic platform, showing strong potential for effective atherosclerosis management.