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

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.

Drug-coated percutaneous balloon catheters.

Percutaneous transluminal angioplasty revolutionized coronary and peripheral revascularization. However, it is always accompanied by major drawbacks such as elastic recoil and neointimal hyperplasia. Percutaneous transluminal angioplasty along with bare metal stents reduced elastic recoil, but in-stent restenosis (ISR) and peripheral artery stenting remain problems. Drug-eluting stents addressed the issue of ISR, but late stent thrombosis and delayed endothelialization, along with longer dual antiplatelet therapy, are of concern. Non-stent-based delivery such as drug-coated balloons (DCBs) that can deliver drugs to inhibit ISR or to de novo lesions, are emerging at a rapid pace. DCBs carry an active drug and a nonpolymeric carrier molecule or excipient that enhance the bioavailability of the drug to the vessel wall. Preliminary studies of paclitaxel show sustained delivery is not required to inhibit proliferation of vascular smooth muscle cells, which leds to the development and evolution of DCBs. Recent clinical trials have been successful in mitigating ISR in coronary and peripheral arteries, but not in de novo lesions of coronary arteries. Clinical studies, although limited to date, show a promising future for DCBs.