OBJECTIVE: @entity1205 ( @entity4420 ) is a novel microtubule polymerizing agent, with superior antiproliferative properties as compared to @entity1311 . @entity4420 is therefore a potential therapeutic tool for the prevention of @entity256 following angioplasty. However, @entity4420 has systemic @entity137 such as @entity1431 , which occurs in a dose-dependent manner. To minimize such adverse effects, we carried out local delivery of low-dose @entity4420 directly to injured vessel sites. METHODS: The @entity95 iliac artery was denuded, and then @entity4420 (2 mg) or control vehicle was administered locally 20 min, via a local drug delivery catheter. RESULTS: The levels of @entity4420 in the plasma were within ng/ml range, eliminating hematopoietic side effects. Seven days after the local delivery ( @entity4420 : n=4, control: n=4), @entity4420 decreased the number of Ki-67-labeled cells in the intima ( @entity4420 : 22 +/-10 vs. control: 66 +/- 18 cells/mm(2), P<0.01), indicating a decreased proliferative activity. At 28 days ( @entity4420 : n=8, control: n=8), computer-assisted morphometric analysis demonstrated that @entity4420 significantly reduced the intimal area ( @entity4420 : 0.15 +/- 0.13 vs. control: 0.70 +/- 0.13 mm(2), P<0.01). There was also a decrease in medial area in the @entity4420 -treated vessels ( @entity4420 : 0.62 +/- 0.17 vs. control: 1.13 +/- 0.38 mm(2), P<0.01). CONCLUSIONS: Local delivery of @entity4420 , even after a single low-dose administration, effectively inhibits neointimal @entity1373 . Such administration is associated with a minimal likelihood of @entity4237 ( @entity1431 ), but potentially induces local @entity137 (a decrease in medial wall thickness) due to extensive cytotoxic effect.

Local delivery of low-dose @entity1205 , a novel microtubule polymerizing agent, reduces neointimal XXXX in a balloon-injured @entity95 iliac artery model.

@entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity1373 :: ('MESH:D006965', 'Disease') :: ['hyperplasia'] @entity1311 :: ('MESH:D017239', 'Chemical') :: ['paclitaxel'] @entity256 :: ('MESH:D023903', 'Disease') :: ['restenosis'] @entity95 :: ('9986', 'Species') :: ['rabbit'] @entity4237 :: ('MESH:D000160', 'Disease') :: ['systemic adverse effects'] @entity1431 :: ('MESH:D007970', 'Disease') :: ['leukocytopenia'] @entity1205 :: ('MESH:C067311', 'Chemical') :: ['Docetaxel'] @entity4420 :: ('CHEBI:16973', 'Chemical') :: ['DOC']
@entity1373 :: (MESH:D006965,Disease) :: ['hyperplasia']
