Application of Nanoparticle Technology for the Prevention of Restenosis After Balloon Injury in Rats

Abstract

Abstract-Restenosis after percutaneous coronary intervention continues to be a serious problem in clinical cardiology.Recent advances in nanoparticle technology have enabled us to deliver an antiproliferative drug selectively to the balloon-injured artery for a longer time. NK911, which is a core-shell nanoparticle of polyethyleneglycol-based block copolymer encapsulating doxorubicin, accumulates in vascular lesions with increased permeability. We first confirmed that balloon injury caused a marked and sustained increase in vascular permeability (as evaluated by Evans blue staining) for a week in the rat carotid artery. We then observed that intravenous administration of just 3 times of NK911, but not doxorubicin alone, significantly inhibited the neointimal formation of the rat carotid artery at 4 weeks after the injury in both a single-and double-injury model. Immunostaining demonstrated that the effect of NK911 was due to inhibition of vascular smooth muscle proliferation but not to enhancement of apoptosis or inhibition of inflammatory cell recruitment. Measurement of vascular concentrations of doxorubicin confirmed the effective delivery of the agent to the balloon-injured artery by NK911 in both a single-and double-injury model. RNA protection assay demonstrated that NK911 inhibited expression of several cytokines but not that of apoptosis-related molecules. NK911 was well tolerated without any adverse systemic effects. These results suggest that nanoparticle technology to target vascular lesions with increased permeability is a promising and safe approach for the prevention of restenosis after balloon injury.

In vivo prevention of arterial restenosis with paclitaxel-encapsulated targeted lipid–polymeric nanoparticles

“…bolus injection at either 0.3 mg/kg or 1 mg/kg, with five animals per treatment dose. Repeat dosing is noninvasive and may be beneficial in preventing neointimal proliferation (29). To determine the optimal timing for a repeat dose, in vivo pharmacokinetic studies of nanoburrs were performed (Fig.…”

“…Because the animals were also given a repeat dose on day 5, increased collagen deposition may contribute to the antistenotic efficacy observed here. Effective repeat dosing that corresponds to lesion severity may be useful for chronic diseases like atherosclerosis (19,29), which may not always be resolved by revascularization alone (20).…”

A Novel Contrast Medium Detects Increased Permeability of Rat Injured Carotid Arteries in Magnetic Resonance T2 Mapping Imaging

“…In this sense, our contrast medi- um is quite different from other iron nanoparticles that accumulate at the lesion by phagocytosis 14) because a large amount of other iron nanoparticles are required to detect vascular lesions. Finally, this drug delivery system theoretically accommodates both contrast medium and agent for treatment, therefore enabling us to simultaneously detect and treat vascular lesions 25,26) . Furthermore, this particle can be modified to deliver agents to the target tissue more precisely 27) .…”

New applications of nanoparticles in cardiovascular imaging

“…The iron oxide nanoparticles with a payload of imaging contrast agent or a drug or a combination of both, can be used for drug delivery and monitoring by images [1][2][3][4][5][6][7][8][9][10][11][12]. The iron-oxide nanoparticles bound with specific antibody also serve as a targeting system to locate the leached out antigen from the site of myocardial infarction.…”

“…These quantum dots have fluorescent properties useful for fluorescent imaging for cell tracking to assess the efficiency of heart transplantation. Recently, doxorubicin bound NK911 nanoparticles (core-shell nanoparticles of PEG-based block copolymer encapsulating doxorubicin) were reported to inhibit restenosis [1]. The nanoparticles easily permeate through the blood vessels and vascular injury sustains the hyperpermeability.…”