Local Delivery of Imatinib Mesylate (STI571)-Incorporated Nanoparticle Ex Vivo Suppresses Vein Graft Neointima Formation

Kimura, Satoshi; Egashira, Kensuke; Nakano, K.; Iwata, Eiko; Miyagawa, Miho; Tsujimoto, Hiroyuki; Hara, Kaori; Kawashima, Yasunaru; Tominaga, Ryuji; Sunagawa, Kenji

doi:10.1161/circulationaha.107.740613

Cited by 46 publications

(35 citation statements)

References 23 publications

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“…We previously showed that (1) PLGA-NP was taken up actively by VSMC and endothelial cells mainly via endocytosis and was retained stably in the intracellular space and that (2) NPs may slowly release encapsulated drugs as PLGA is hydrolyzed 22,23) This bioabsorbable polymeric NP-eluting stent system has unique aspects with respect to vascular compatibility and efficient drug delivery (stable delivery of NPs into the neointima and medial layers until day 28 after deployment of the NP-eluting stent), as compared to dip-coated polymer-eluting stents 22) . Importantly, this NP drug delivery system can carry hydrophilic agents such as statins, which offer advantages over the current stent-coating technology.…”

Section: Discussionmentioning

confidence: 99%

“…Human coronary artery smooth muscle cells (SMC) were cultured as previously described 22,23) and plated into 96-well culture plates at 1×10 4 cells per well in SMGM2. Proliferation was stimulated by adding human PDGF at 10 ng/mL (Sigma, Tokyo, Japan) or 10% FBS to each well.…”

Section: Human Coronary Artery Smooth Muscle Cell Proliferationmentioning

confidence: 99%

“…Comparator analysis of endothelial cell coverage in four marketed polymeric DESs in rabbits has demonstrated a disparity in arterial healing; notably, all DESs examined showed a lack of endothelial anticoagulant function, independent of endothelial coverage 7) . were determined by evaluating the 5'-bromo-2'-deoxyuridine (BrdU) incorporation rate and/or by a cell counting method, as previously described 22,23) .…”

Section: Introductionmentioning

confidence: 99%

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Pitavastatin-Incorporated Nanoparticle-Eluting Stents Attenuate In-Stent Stenosis without Delayed Endothelial Healing Effects in a Porcine Coronary Artery Model

Tsukie

Nakano

Matoba

et al. 2013

JAT

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Aim:The use of currently marketed drug-eluting stents presents safety concerns including increased late thrombosis, which is thought to result mainly from delayed endothelial healing effects (impaired re-endothelialization resulting in abnormal inflammation and fibrin deposition). We recently developed a bioabsorbable polymeric nanoparticle (NP)-eluting stent using a novel cationic electrodeposition technology. Statins are known to inhibit the proliferation of vascular smooth muscle cells (VSMC) and to promote vascular healing. We therefore hypothesized that statin-incorporated NPeluting stents would attenuate in-stent stenosis without delayed endothelial healing effects. Methods: Among six marketed statins, pitavastatin (Pitava) was found to have the most potent effects on VSMC proliferation and endothelial regeneration in vitro. We thus formulated a Pitava-NP-eluting stent (20 μg Pitava per stent). Results: In a pig coronary artery model, Pitava-NP-eluting stents attenuated in-stent stenosis as effectively as polymer-coated sirolimus-eluting stents (SES). At SES sites, delayed endothelial healing effects were noted, whereas no such effects were observed in Pitava-NP-eluting stent sites. Conclusion: Pitava-NP-eluting stents attenuated in-stent stenosis as effectively as SES without the delayed endothelial healing effects of SES in a porcine coronary artery model. This nanotechnology platform could be developed into a safer and more effective device in the future.

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Section: Discussionmentioning

confidence: 99%

Section: Human Coronary Artery Smooth Muscle Cell Proliferationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pitavastatin-Incorporated Nanoparticle-Eluting Stents Attenuate In-Stent Stenosis without Delayed Endothelial Healing Effects in a Porcine Coronary Artery Model

Tsukie

Nakano

Matoba

et al. 2013

JAT

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“…Therefore, we have tested the effect of nanoparticles encapsulating tyrosine kinase inhibitor of PDGF (platelet-derived growth facor) receptor (Imatinib-NPs). Ex vivo treatments of vein grafts before implantation decreased intimal thickness 51) . In this case, smooth muscle cells took up the nanoparticles after incubating the graft with PLGANPs.…”

Section: Plga Nanoparticles For the Treatments Of Ischemia-reperfusiomentioning

confidence: 95%

Anti-inflammatory Nanoparticle for Prevention of Atherosclerotic Vascular Diseases

Koga

Matoba

Egashira

2016

JAT

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Recent technical innovation has enabled chemical modifications of small materials and various kinds of nanoparticles have been created. In clinical settings, nanoparticle-mediated drug delivery systems have been used in the field of cancer care to deliver therapeutic agents specifically to cancer tissues and to enhance the efficacy of drugs by gradually releasing their contents. In addition, nanotechnology has enabled the visualization of various molecular processes by targeting proteinases or inflammation. Nanoparticles that consist of poly (lactic-co-glycolic) acid (PLGA) deliver therapeutic agents to monocytes/macrophages and function as anti-inflammatory nanoparticles in combination with statins, angiotensin receptor antagonists, or agonists of peroxisome proliferator-activated receptor-(PPAR ). PLGA nanoparticle-mediated delivery of pitavastatin has been shown to prevent inflammation and ameliorated features associated with plaque ruptures in hyperlipidemic mice. PLGA nanoparticles were also delivered to tissues with increased vascular permeability and nanoparticles incorporating pitavastatin, injected intramuscularly, were retained in ischemic tissues and induced therapeutic arteriogenesis. This resulted in attenuation of hind limb ischemia. Ex vivo treatment of vein grafts with imatinib nanoparticles before graft implantation has been demonstrated to inhibit lesion development. These results suggest that nanoparticle-mediated drug delivery system can be a promising strategy as a next generation therapy for atherosclerotic vascular diseases. nm. In tumor tissues or at the site of inflammation, the integrity of these endothelial layers is impaired and the nanoparticles can extravasate to the extravascular space through the enlarged interspace between endothelial cells. In tumor tissues, immature lymphatic vessels retard elimination of nanoparticles. These effects are known as enhanced permeability and retention effects 22,23) . Surface modification with polyethylene glycol (PEG) prevents entrapment of nano particles by the reticuloendothelial system due to its hydrophilic property. Therefore, these nanoparticles are called stealth nanoparticles 24,25) . J Atheroscler Nanoparticles as a Research Tool for AtherosclerosisClinical applications of nanoparticles are advanced in the field of diagnostic medicine. For example, magnetic nanoparticles with iron cores are available in MRI for macrophage imaging 26) . These so-called superparamagnetic iron oxide (SPIO) nanoparticles are used as a negative contrast agent in MRI. The iron core is modified with hydrophilic polymers including dextran, carboxymethylated dextran, polyvinyl alcohol, starches, chitosan, polymethyl methacrylate, PEG, poly (lactic-co-glycolic) acid (PLGA), polyvinylpyrrolidone, and polyacrylic acid 27) . These particles have been tested in patients to evaluate inflammation, plaque vulnerability, and therapeutic effects of lipid lowering drugs, especially in the carotid arteries of patients 26,28,29) . Adhesion molecules are also targets of molecu...

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“…We previously reported (1) the in vitro time course of FITC release from FITC-incorporated NP, and (2) highly efficient and stable delivery of NP into the cytoplasm of SMC and endothelial cells 19,21,26,27) . In the present study, we examined in vitro effects of imatinib and imatinib-NP.…”

Section: In Vitro Effects Of Imatinib On Proliferation Of Vascular Smmentioning

confidence: 99%

Imatinib Mesylate-Incorporated Nanoparticle-Eluting Stent Attenuates In-Stent Neointimal Formation in Porcine Coronary Arteries

Masuda

Nakano

Funakoshi

et al. 2011

JAT

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Aim:The use of currently marketed drug-eluting stents (DES) presents safety concerns, including an increased risk for late thrombosis in the range of 0.6% per year in patients, including acute coronary syndrome, which is thought to result from delayed endothelial healing effects. A new DES system targeting vascular smooth muscle cells without adverse effects on endothelial cells is therefore needed. Platelet-derived growth factor (PDGF) plays a central role in the pathogenesis of restenosis; therefore, we hypothesized that imatinib mesylate (PDGF receptor tyrosine kinase inhibitor) encapsulated bioabsorbable polymeric nanoparticle (NP)-eluting stent attenuates in-stent neointima formation. Methods: Effects of imatinib-incorporated NP-eluting stent on neointima formation and endothelial healing were examined in a pig coronary artery stent model. Effects of imatinib-NP were also examined in cultured cells. Results: In a cultured cell study, imatinib-NP attenuated the proliferation of vascular smooth muscle cells associated with inhibition of the target molecule (phosphorylation of PDGF receptor-), but showed no effect on endothelial proliferation. In a pig coronary artery stent model, imatinib-NPeluting stent markedly attenuated in-stent neointima formation and stenosis by approximately 50% as assessed by angiographic, histopathological, and intravascular ultrasound imaging analyses. Imatinib-NP-eluting stent also attenuated MAP kinase activity, but did not affect inflammation and re-endothelialization. Conclusion: These data suggest that suppression of neointima formation by a imatinib-NP-eluting stent holds promise as a molecular-targeting NP delivery system for preventing in-stent restenosis.

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Local Delivery of Imatinib Mesylate (STI571)-Incorporated Nanoparticle Ex Vivo Suppresses Vein Graft Neointima Formation

Cited by 46 publications

References 23 publications

Pitavastatin-Incorporated Nanoparticle-Eluting Stents Attenuate In-Stent Stenosis without Delayed Endothelial Healing Effects in a Porcine Coronary Artery Model

Pitavastatin-Incorporated Nanoparticle-Eluting Stents Attenuate In-Stent Stenosis without Delayed Endothelial Healing Effects in a Porcine Coronary Artery Model

Anti-inflammatory Nanoparticle for Prevention of Atherosclerotic Vascular Diseases

Imatinib Mesylate-Incorporated Nanoparticle-Eluting Stent Attenuates In-Stent Neointimal Formation in Porcine Coronary Arteries

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