Gradus-Pizlo I, Wilensky R L, March K L, Fineberg N, Michaels M, Sandusky G E, Hathaway D R
Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis 46202-4800, USA.
J Am Coll Cardiol. 1995 Nov 15;26(6):1549-57. doi: 10.1016/0735-1097(95)00345-2.
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.
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.
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).
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.
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.
本研究旨在评估血管成形术后将可溶性秋水仙碱或秋水仙碱类似物输送至动脉壁的递送效率、壁内滞留情况及抗再狭窄疗效，以及这些药物从可生物降解微粒中长时间局部释放后的疗效。
局部递送药理剂是治疗再狭窄的一种潜在方法。然而，该技术的递送效率以及调节细胞增殖的药剂选择尚不清楚。据推测，再狭窄不会受到秋水仙碱或壁内滞留时间短的疏水性秋水仙碱类似物的影响，而在长时间局部释放后再狭窄会减轻。
对兔动脉粥样硬化股动脉进行血管成形术，随后进行局部递送。评估³H-秋水仙碱的递送效率和壁内滞留情况。在2周时评估可溶性制剂或从微粒中释放的药剂对血管造影和形态学再狭窄的影响，并与对照组（仅血管成形术和局部输注载体溶液）进行比较。
递送效率为0.01%，壁内滞留时间<24小时。可溶性秋水仙碱制剂均未减轻再狭窄。与对照组和秋水仙碱微粒相比，释放秋水仙碱类似物的微粒减轻了再狭窄，但与单纯血管成形术相比无差异（p = 0.002）。观察到动脉外有递送情况，且两种秋水仙碱的长期释放均导致对相邻肌肉组织的毒性。
秋水仙碱或秋水仙碱类似物未减轻再狭窄，尽管秋水仙碱类似物的长期局部释放减少了局部递送导致的新生内膜增殖。血管特异性不足的细胞毒性剂的局部递送可能会因递送面积大于预期和药剂滞留时间延长而对相邻组织产生毒性而受到限制。
