Sirolimus-loaded stealth colloidal systems attenuate neointimal hyperplasia after balloon injury: A comparison of phospholipid micelles and liposomes

Restenosis after angioplasty remains a serious complication in clinical cardiology. This study aims to investigate the stealth colloidal systems for local intra-arterial drug delivery. Micelles from polyethylene glycol conjugated with phosphatidylethanolamine and PEGylated liposomes loaded with sirolimus were prepared and characterized with regard to their loading efficiency, particle size distribution, zeta potential, morphology, nuclear magnetic resonance spectroscopy, drug release profile and stability. The antirestenotic effects of the sirolimus-loaded micelles (14 nm) and liposomes (90 nm) were evaluated and compared in the rat carotid injury model following local intravascular delivery. In comparison to control groups, treatment of balloon injured rats with drug loaded micelles and nanoliposomes significantly reduced vascular stenosis by 42% and 19%, respectively (P < 0.05). In addition, the luminal area was significantly enlarged by 39% and 60% following treatment with sirolimus-loaded liposomes and micelles, respectively (P < 0.05). Immunohistochemistry revealed that sirolimus-loaded nanocarriers suppressed cell proliferation (Ki67-positive cells) as compared to control groups without affecting the density of smooth muscle actin staining. These results suggest that both colloidal nanocarriers could serve as effective intramural drug delivery systems for the treatment of restenosis; however, phospholipid based micelles provided better antirestenotic effects than PEGylated liposomes.

%Stenosis and number of Ki67 positive cells (indicative of proliferation) were significantly reduced by local therapy with sirolimus-loaded micelles and liposomes. Small phospholipid micelles provided better antirestenotic effects than larger stealth liposomes.Figure optionsDownload high-quality image (221 K)Download as PowerPoint slide