Table 4.
Illustrative examples of nanoparticulate carrier-based gene delivery in restenosis
| Genes | Nanocarrier System | Model and Route of Administration | Conclusions | Reference(s) |
|---|---|---|---|---|
| Endothelial nitric oxide synthase (eNOS) | Cationic Liposomes (Lipofectamine plus) | Adult male mongrel dogs, ex-vivo saphenous vein transfection, both intimal and adventitial. | No efficient gene transcription with intimal transfection, adventitial transfection showed elevated mRNA levels compared to controls. | (Kalra et al 2000) |
| PCNA chimeric hammerhead ribozyme | Cationic liposomes (Lipofectamine/Lipofectin) | Balloon injured porcine coronary artery | Inhibition of intimal hyperplasia and reduction of coronary artery restenosis | (Frimerman et al 1999) |
| Prostacyclin synthase (PGIS) | Cationic liposomes (Lipofectamine) | Balloon injured and stented New Zealand White rabbits with local delivery using Dispatch® catheter. | PGIS induced PGI2 expression and inhibited VSMC growth and accelerated re-endothelialization, preventing neointimal formation | (Numaguchi et al 2004) |
| hRAD50 | Nonliposomal lipid (FuGENE 6, Boehringer Mannheim) | Coronary stented porcine model, local delivery using Dispatch® catheter | Regression of established neointimal hyperplasia after coronary stenting. | (Ahn et al 2004) |
| Inducible nitric oxide synthase (iNOS) | DAC (30% w/w) and DOPE (70% w/w) | Coronary and femoral artery stented mini pigs, local administration of lipoplex with Infiltrator® catheter. | Inhibition of intimal hyperplasia. | (Muhs et al 2003) |
| Inducible nitric oxide synthase (iNOS) | Cationic liposomes | Grafted foxhound dogs carotid artery bypass grafts, local delivery using Infiltrator® catheter | Single transfection able to show inhibition of intimal growth for up to 6 months. | (Pfeiffer et al 2006) |
| Endothelial nitric oxide synthase (eNOS) | Cationic liposomes | Human umbilical vein endothelial cell (ECV304) in vitro | Successful transfer of eNOS in-vitro, saw increase in NO. | (Qiao et al 2006) |
| Endothelial nitric oxide synthase (eNOS)) | Liposomes/cationic liposomes | New Zealand white rabbits and Stauffland rabbits heart transplants, liposomes delivered ex-vivo to aortic roots of donor heart | Despite transfection inefficiencies with liposomes, measurable NO expression was achieved, reducing endothelial activation | (Iwata et al 2000; Iwata et al 2001) |
| Chloramphenicol acetyl transferase (CAT) | Cationic liposomes | Balloon injured Yorkshire pig iliofemoral arteries, local delivery using catheter. | Saw increased CAT activity after liposome transfection in artery. | (Stephan et al 1996) |
| C-type natriuretic peptide (CNP) | Cationic liposomes DOCSPER, (1,3-dioleoyloxy-2-(N5-carbamoyl-spermine)-propane) | Porcine renal artery and pig femoral arteries, percutaneous introduced needle injector catheter used to locally deliver drug | Successful inhibition of renal artery restenosis and femoral artery restenosis. | (Kuhnl et al 2005; Pelisek et al 2006) |
| Vascular endothelial growth factor (VEGF) | Cationic liposomes | Human trial containing patients with angina and 60–99% diameter stenosis in 1–2 of main coronary arteries. Local delivery achieved using Dispatch catheter. | Did not affect post angioplasty restenosis, but significant improvement in myocardial perfusion was observed in viral vector treated patients | (Hedman et al 2003) |
| E2F oligonucleotide decoy | Hemaglutin virus of Japan (HVJ) liposomes | B10.D2 mice and Japanese monkeys hearts were treated ex-vivo prior to transplant with viral liposomes | Ex vivo liposomal transfection suppressed neointimal hyperplasia after cardiac transplant surgery | (Kawauchi et al 2000) |
| E2F oligonucleotide decoy | Hemaglutin virus of Japan (HVJ) liposomes | Balloon denuded rat carotid artery, local delivery using catheter | Neointima inhibition seen up to 8 weeks after single intraluminal injection | (Morishita et al 1995) |
| Wild type p53 | Hemaglutin virus of Japan (HVJ) liposomes | Balloon denuded Japanese white rabbits with local delivery using double-lumen catheter | p53 Gene transfer inhibits neointimal formation without apoptotic stimuli. VSMC growth inhibited. | (Yonemitsu et al 1998) |
| Tissue factor pathway inhibitor gene | Hemaglutin virus of Japan (HVJ) liposomes | High cholesterol fed rabbit model. Illiac artery, balloon angioplasty was used to open stenosis, local liposome delivery using Dispatch catheter. | Significant reduction of intimal hyperplasia compared to controls, confirmed through histology and angiography. | (Yin et al 2002) |
| Prostacyclin synthase (PGIS) | Hemaglutin virus of Japan (HVJ) liposomes | Balloon denuded Sprawly rat carotid artery, local delivery using infusion catheter. | PGIS expression in neointima, inhibiting neointimal growth. | (Todaka et al 1999) |
| Platelet derived growth factor (PDGF) receptor β-antisense | PLGA nanoparticles | Explanted rat SMC in-vitro, injured rat carotid artery in-vivo | Controlled release of oligonucleotide over 1 month, neointima growth inhibited in naked AS and PLGA NP AS, PLGA NP believed to be effective at lower concentrations, due to sustained release. | (Cohen-Sacks et al 2002) |
| Monocyte chemoattractant protein 1 (MCP-1) | PEI, PEI / PEG, PEI / mellatin | In-vitro in SMC and EC | Inhibition of SMC growth, incorporation of mellatin increased activity, while decreasing toxicity | (Lenter et al 2004) |
| Early growth response factor 1 (EGR-1) | DNAzyme | Porcine coronary stent model, local delivery with Transport catheter | Inhibition of SMC and reducing in-stent restenosis. | (Lowe et al 2001) |