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Local delivery of sirolimus nanoparticles for the treatment of in‐stent restenosis
Author(s) -
Zago Alexandre C.,
Raudales José C.,
Attizzani Guilherme,
Matte Bruno S.,
Yamamoto German I.,
Balvedi Julise A.,
Nascimento Ludmila,
Kosachenco Beatriz G.,
Centeno Paulo R.,
Zago Alcides J.
Publication year - 2013
Publication title -
catheterization and cardiovascular interventions
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.988
H-Index - 116
eISSN - 1522-726X
pISSN - 1522-1946
DOI - 10.1002/ccd.24331
Subject(s) - medicine , restenosis , stent , intravascular ultrasound , sirolimus , neointima , angioplasty , ferumoxytol , cardiology , radiology , magnetic resonance imaging
Objectives To test the local delivery of sirolimus nanoparticles following percutaneous transluminal coronary angioplasty (PTCA) to treat in‐stent restenosis (ISR) in a swine model. Background Coronary bare‐metal stent (BMS) implantation reduces major adverse cardiac events when compared with PTCA; however, ISR rates remain high. Methods Eighteen swine underwent BMS deployment guided by intravascular ultrasound (IVUS). Of these, 16 developed ISR (1 stent/swine) and underwent angioplasty with a noncompliant balloon (PTCA‐NC). The animals were then randomized into four groups for local infusion of sirolimus nanoparticles through a porous balloon catheter, as follows: (1) PTCA‐NC alone (control); (2) PTCA‐NC + (polylactic acid)‐based nanoparticle formulation (anionic 1); (3) PTCA‐NC + (polylactic‐co‐glycolic acid)‐based nanoparticle formulation (anionic 2); and (4) PTCA‐NC + Eudragit RS nanoparticle formulation (cationic). Coronary angiography and IVUS follow‐up were performed 28 days after ISR treatment. Results There was one episode of acute coronary occlusion with the cationic formulation. Late area loss was similar in all groups at 28 days according to IVUS. However, luminal volume loss (control = 20.7%, anionic 1 = 4.0%, anionic 2 = 6.7%, cationic = 9.6%; P = 0.01) and neointimal volume gain (control = 68.7%, anionic 1 = 17.4%, anionic 2 = 29.5%, cationic = 31.2%; P = 0.019) were significantly reduced in all treatment groups, especially in anionic 1. Conclusions PTCA‐NC followed by local infusion of sirolimus nanoparticles was safe and efficacious to reduce neointima in this model, and this strategy may be a promising treatment for BMS ISR. Further studies are required to validate this method in humans. © 2012 Wiley Periodicals, Inc.