Green formulation of curcumin loaded lipid-based nanoparticles as a novel carrier for inhibition of post-angioplasty restenosis

Abstract

Restenosis is one of the major complications affecting outcomes of percutaneous coronary interventions. The aims of this study were to formulate curcumin (CUR) nanoparticles by using only lipidic ingredients in the absence of any organic solvent and to determine key formulation parameters using 2-level factorial design. CUR nanoparticles were prepared using triglyceride and egg phosphatidylcholine (EPC) by high-pressure homogenization (HPH) and fully characterized regarding drug loading, particle size, zeta potential, stability, drug release profile, conductivity, viscosity, refractive index, stability, morphology and FTIR analysis. The efficacy of CUR nanoparticles in inhibiting restenosis was investigated in a rat carotid artery model. Balloon-injured rats were randomly assigned to two control (saline and empty carrier) groups and CUR nanoparticle treated group. Arterial restenosis was assessed by histomorphometric, immunohistochemical and CT angiography analyses. Optimized CUR nanoparticles with almost 70% drug entrapment, an average particle size of 58 nm, PDI < 0.2, spherical nanostructures and sustained release profile were prepared. In morphometric analysis, neointimal area and neointima/media ratio significantly decreased in the animal group received CUR nanoparticles compared with control groups. Expression of Ki67 was markedly lower in the CUR nanoformulation group. CT angiograms confirmed patency of the artery in this group. These results suggest that the new strategy of intramural delivery of CUR lipid-based nanoparticles can be considered as a novel approach to prevent neointimal hyperplasia.

Keywords: Balloon angioplasty; Curcumin; Green formulation; Lipid-based nanoparticles; Local administration; Restenosis.