Targeted and safe delivery of colchicine via polymeric nanocarriers for potential atherosclerosis therapy with in vitro and in vivo evaluation.

This study highlights the potential of nanoparticle-encapsulated colchicine as a safer and more effective alternative to free colchicine for treating atherosclerotic vascular disease (ASCVD). While colchicine is known for its anti-inflammatory properties, its dose-dependent toxicity limits long-term clinical use. To address this issue, colchicine was encapsulated in polymeric nanoparticles synthesized through a microfluidic method using methylated β-cyclodextrin as the initiator. The resulting formulation achieved an encapsulation efficiency of 30% and a drug loading capacity of 75%, indicating a high payload capability. This approach not only demonstrated high drug-loading efficiency but also enabled controlled release, with approximately 60% of the drug being released over 96 h. The nanoparticle formulation preserved colchicine's ability to inhibit foam cell formation-a critical event in the progression of atherosclerosis-while significantly reducing toxicity to eukaryotic cells. Transmission electron microscopy revealed that cells treated with nanoparticle-bound colchicine maintained normal morphology, unlike those exposed to free colchicine, which rapidly accumulates intracellularly and disrupts cell function. In vivo evaluation confirmed the safety of the formulation, showing no adverse effects on the liver, kidneys, or heart, as indicated by stable levels of ALT, AST, creatinine, and cardiac troponin I. Biodistribution studies with fluorescently labeled nanoparticles further suggested accumulation in tissues such as the heart and liver, highlighting the potential therapeutic relevance of colchicine-loaded nanoparticles for cardiovascular applications. Given these findings, the nanoparticle-based colchicine formulation presents a favorable efficacy and safety profile, warranting further preclinical development and eventual clinical evaluation.