Key result
Colchicine analogue microparticles reduce post-angioplasty restenosis vs carrier control, but fail vs angioplasty alone.
Why the study?
Local delivery of pharmacologic agents is a potential treatment for restenosis, but the delivery efficiency of the technique and the optimal agent to modulate cellular proliferation were unknown.
Does local delivery of soluble or microparticle-encapsulated colchicine or a colchicine analogue reduce angiographic and morphometric restenosis in rabbit atherosclerotic femoral arteries undergoing angioplasty?
Does local delivery of soluble or microparticle-encapsulated colchicine or a colchicine analogue reduce angiographic and morphometric restenosis in rabbit atherosclerotic femoral arteries undergoing angioplasty?
In a rabbit angioplasty model, local catheter-based delivery of colchicine or a colchicine analogue failed to reduce restenosis compared to angioplasty alone and caused adjacent muscle toxicity when released over the long term from microparticles.
Local colchicine analogue delivery fails with toxicity in atherosclerotic arteries; leaves open whether refined carriers can achieve sustained intramural retention.
Objectives This study sought to evaluate the delivery efficiency, intramural retention and antirestenotic efficacy of soluble colchicine or colchicine analogue delivered into the arterial wall after angioplasty as well as the efficacy of these medications after prolonged local release from biodegradable microparticles. Background Local delivery of pharmacologic agents is a potential treatment for restenosis. However, the delivery efficiency of the technique and the choice of agent to modulate cellular proliferation are unknown. It was hypothesized that restenosis would be unaffected by colchicine or a hydrophobic colchicine analogue with short intramural retention, whereas it would be reduced after prolonged local release. Methods Rabbit atherosclerotic femoral arteries underwent angioplasty followed by local delivery. Delivery efficiency and intramural retention of 3H-colchicine were evaluated. The effect of agents in soluble formulation or released from microparticles on angiographic and morphometric restenosis was evaluated at 2 weeks and compared with that in the control groups (angioplasty only and local infusion of carrier solution). Results Delivery of efficiency was 0.01% and intramural retention < 24 h. Neither soluble colchicine formulation reduced restenosis. Microparticles releasing the colchicine analogue reduced restenosis compared with control and colchicine microparticles but not angioplasty alone (p = 0.002). Delivery outside the artery was observed, and the long-term release of both colchicine resulted in toxicity to the adjacent musculature. Conclusions Colchicine or the colchicine analogue did not reduce restenosis, although the long-term local release of the colchicine analogue reduced neointimal proliferation resulting from local delivery. Local delivery of cytotoxic agents with insufficient vascular specificity may be limited by toxicity to adjacent tissues resulting from a larger than expected delivery area and prolonged agent retention.
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Gradus‐Pizlo et al. (1995) studied Atherosclerosis and post-angioplasty restenosis. Local delivery of soluble or biodegradable microparticle-encapsulated colchicine or colchicine analogue vs. Angioplasty only and local infusion of carrier solution was evaluated on Angiographic and morphometric restenosis at 2 weeks (p=0.002). Microparticles releasing a colchicine analogue reduced restenosis vs carrier control and colchicine microparticles (p=0.002), but not vs angioplasty alone, with 0.01% delivery efficiency.
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