title: Local delivery of sirolimus nanoparticles for the treatment of in-stent restenosis.
abstract: OBJECTIVE
  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.
authors.affiliation: Cardiovascular Research Center, Universidade Luterana do Brasil, Canoas, Rio Grande do Sul, Brazil. zagoac@uol.com.br
authors.forename: Alexandre C
authors.initials: AC
authors.lastname: Zago
authors.forename: José C
authors.initials: JC
authors.lastname: Raudales
authors.forename: Guilherme
authors.initials: G
authors.lastname: Attizzani
authors.forename: Bruno S
authors.initials: BS
authors.lastname: Matte
authors.forename: German I
authors.initials: GI
authors.lastname: Yamamoto
authors.forename: Julise A
authors.initials: JA
authors.lastname: Balvedi
authors.forename: Ludmila
authors.initials: L
authors.lastname: Nascimento
authors.forename: Beatriz G
authors.initials: BG
authors.lastname: Kosachenco
authors.forename: Paulo R
authors.initials: PR
authors.lastname: Centeno
authors.forename: Alcides J
authors.initials: AJ
authors.lastname: Zago
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D062906:Cardiac Catheters; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000000981:diagnostic imaging / Q000628:therapy*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects*; D004195:Disease Models, Animal; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004867:Equipment Design; D007263:Infusions, Parenteral; D019344:Lactic Acid / Q000737:chemistry; D053758:Nanoparticles; D058426:Neointima; D062645:Percutaneous Coronary Intervention; D011091:Polyesters; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D016062:Porosity; D020123:Sirolimus / Q000008:administration & dosage* / Q000737:chemistry; D013552:Swine; D013997:Time Factors; D018084:Ultrasonography, Interventional
chemical_list: D000180:Acrylic Resins; D002317:Cardiovascular Agents; D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; C050528:Eudragit RS; D019344:Lactic Acid; C033616:poly(lactide); D020123:Sirolimus