title: Biological effect on restenosis and vascular healing of encapsulated paclitaxel nanocrystals delivered via coated balloon technology in the familial hypercholesterolaemic swine model of in-stent restenosis.
abstract: OBJECTIVE
  The aim of this study was to evaluate the biological efficacy of a novel lower-dose (2.5 µg/mm2) encapsulated paclitaxel nanocrystal-coated balloon (Nano-PCB) in the familial hypercholesterolaemic swine (FHS) model of iliofemoral in-stent restenosis.
  
  
  RESULTS
  Nano-PCB pharmacokinetics were assessed in 20 femoral arteries (domestic swine). Biological efficacy was evaluated in ten FHS: 14 days following bare metal stent implantation each stent segment was randomised to a clinically available PCB (IN.PACT, n=14), the Nano-PCB (n=14) or an uncoated balloon (n=12). Angiographic, optical coherence tomography and histological evaluation was performed at 28 days after treatment. Arterial paclitaxel concentration was 120.7 ng/mg at one hour and 7.65 ng/mg of tissue at 28 days with the Nano-PCB. Compared to the control uncoated group, both PCBs significantly reduced percent area stenosis (Nano-PCB: 36.0±14.2%, IN.PACT: 29.3±9.2% vs control: 67.9±15.1%, p<0.001). Neointimal distribution in the entire stent length was more homogenous in the Nano-PCB. Histological evaluation showed comparable degrees of neointimal proliferation in both PCBs; however, the Nano-PCB showed slightly higher levels of neointimal maturity and endothelialisation.
  
  
  CONCLUSIONS
  Lower-dose encapsulated paclitaxel nanocrystals delivered via a coated balloon displayed comparable biological efficacy with superior healing features compared to a clinically validated PCB technology.
authors.affiliation: CRF Skirball Center for Innovation, Orangeburg, NY, USA.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Cheng
authors.forename: Masahiko
authors.initials: M
authors.lastname: Shibuya
authors.forename: Jenn
authors.initials: J
authors.lastname: McGregor
authors.forename: Gerard B
authors.initials: GB
authors.lastname: Conditt
authors.forename: Geng-Hua
authors.initials: GH
authors.lastname: Yi
authors.forename: Greg L
authors.initials: GL
authors.lastname: Kaluza
authors.forename: William
authors.initials: W
authors.lastname: Gray
authors.forename: Manish
authors.initials: M
authors.lastname: Doshi
authors.forename: Prakash
authors.initials: P
authors.lastname: Sojitra
authors.forename: Juan F
authors.initials: JF
authors.lastname: Granada
mesh_terms: D000792:Angiography; D015906:Angioplasty, Balloon, Coronary / Q000295:instrumentation; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D006083:Graft Occlusion, Vascular; D006938:Hyperlipoproteinemia Type II; D007083:Iliac Artery / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D008670:Metals; D053758:Nanoparticles / Q000008:administration & dosage; D058426:Neointima; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D016491:Peripheral Vascular Diseases; D015607:Stents; D034421:Sus scrofa; D013552:Swine; D041623:Tomography, Optical Coherence; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D008670:Metals; D017239:Paclitaxel