Combinatorial therapy of sirolimus and heparin by nanocarrier inhibits restenosis after balloon angioplasty ex vivo.

ABSTRACT

Aim: To develop poly(lactide-co-glycolide)-graft-polyethylenimine (PgP) as a dual drug-delivery carrier for sirolimus (SR) and heparin (Hep) to inhibit restenosis after balloon angioplasty. Materials & methods: SR was loaded in the hydrophobic core and negatively charged Hep complexed with the positively charged hydrophilic shell of PgP. SR- and Hep-loaded PgP was tested on rat aortic smooth muscle cells in vitro and injured porcine coronary arteries after balloon angioplasty ex vivo. Results & conclusion: SR and Hep loading efficiency in PgP were approximately 37 and 82%, respectively. SR- and Hep-loaded PgP treatment decreased smooth muscle cell proliferation up to 14 days post-treatment and decreased proliferation, collagen deposition and neointimal thickness and increased patency in porcine coronary arteries after balloon angioplasty ex vivo.