Efficiency of dispatch® and infiltrator® cardiac infusion catheters in arterial localisation of nanoparticles in a porcine coronary model of restenosis

J. Panyam, J. Lof, Edward Lewis O'Leary, V. Labhasetwar

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Localized intramural delivery of sustained release biodegradable nanoparticles containing an antiproliferative agent could provide prolonged drug effect at the site of vascular injury that could inhibit the proliferation of smooth muscle cells and hence restenosis. The efficiency of arterial localization of nanoparticles is crucial in maximizing the drug effect in the target tissue. Therefore, the objective of the present study was to determine the comparative efficiency of the Dispatch® and the Infiltrator® cardiac infusion catheters to localize nanoparticles in the arterial wall. Following a standard balloon angioplasty procedure on the left anterior descending artery (LAD) in a porcine coronary model of restenosis, a suspension of nanoparticles containing a fluorescent marker was infused at the site of injury using either the Dispatch® or the Infiltrator® catheter. One hour following the infusion, animals were sacrificed and the nanoparticle levels in the LAD and other tissue were analyzed. The Dispatch® catheter resulted in 3.3 folds greater efficiency of nanoparticle localization in the LAD than the Infiltrator® catheter (309 ± 124 vs. 93 ± 43 μg/g of tissue, n = 6 for Dispatch® and n = 5 for Infiltrator®, p = 0.082, t-test). It is estimated that about 2% of the arterial volume can be displaced with the nanoparticle infusion. Fluorescence microscopy of the cross-sections of the LAD revealed greater fluorescence activity in the intimal layer with both the catheters, however the arteries infused using the Dispatch® catheter demonstrated relatively higher degree of fluorescence activity in the medial and adventitial layers. The transmission electron microscopy of the arterial sections demonstrated infiltration of nanoparticles in the arterial wall and the histological analysis of the sections demonstrated no apparent damage to the endothelium due to the infusion of nanoparticles.

Original languageEnglish (US)
Pages (from-to)515-523
Number of pages9
JournalJournal of Drug Targeting
Volume10
Issue number6
DOIs
StatePublished - Sep 1 2002

Fingerprint

Coronary Restenosis
Cardiac Catheters
Nanoparticles
Swine
Catheters
Arteries
Fluorescence
Tunica Intima
Adventitia
Balloon Angioplasty
Vascular System Injuries
Transmission Electron Microscopy
Fluorescence Microscopy
Pharmaceutical Preparations
Smooth Muscle Myocytes
Endothelium
Suspensions

Keywords

  • Local delivery
  • Restenosis
  • Site-specific therapy
  • Sustained release

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Efficiency of dispatch® and infiltrator® cardiac infusion catheters in arterial localisation of nanoparticles in a porcine coronary model of restenosis. / Panyam, J.; Lof, J.; O'Leary, Edward Lewis; Labhasetwar, V.

In: Journal of Drug Targeting, Vol. 10, No. 6, 01.09.2002, p. 515-523.

Research output: Contribution to journalArticle

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abstract = "Localized intramural delivery of sustained release biodegradable nanoparticles containing an antiproliferative agent could provide prolonged drug effect at the site of vascular injury that could inhibit the proliferation of smooth muscle cells and hence restenosis. The efficiency of arterial localization of nanoparticles is crucial in maximizing the drug effect in the target tissue. Therefore, the objective of the present study was to determine the comparative efficiency of the Dispatch{\circledR} and the Infiltrator{\circledR} cardiac infusion catheters to localize nanoparticles in the arterial wall. Following a standard balloon angioplasty procedure on the left anterior descending artery (LAD) in a porcine coronary model of restenosis, a suspension of nanoparticles containing a fluorescent marker was infused at the site of injury using either the Dispatch{\circledR} or the Infiltrator{\circledR} catheter. One hour following the infusion, animals were sacrificed and the nanoparticle levels in the LAD and other tissue were analyzed. The Dispatch{\circledR} catheter resulted in 3.3 folds greater efficiency of nanoparticle localization in the LAD than the Infiltrator{\circledR} catheter (309 ± 124 vs. 93 ± 43 μg/g of tissue, n = 6 for Dispatch{\circledR} and n = 5 for Infiltrator{\circledR}, p = 0.082, t-test). It is estimated that about 2{\%} of the arterial volume can be displaced with the nanoparticle infusion. Fluorescence microscopy of the cross-sections of the LAD revealed greater fluorescence activity in the intimal layer with both the catheters, however the arteries infused using the Dispatch{\circledR} catheter demonstrated relatively higher degree of fluorescence activity in the medial and adventitial layers. The transmission electron microscopy of the arterial sections demonstrated infiltration of nanoparticles in the arterial wall and the histological analysis of the sections demonstrated no apparent damage to the endothelium due to the infusion of nanoparticles.",
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