Poly(N-isopropylacrylamide) co-polymer films as potential vehicles for delivery of an antimitotic agent to vascular smooth muscle cells
Poly(N-isopropylacrylamide) co-polymer films as potential vehicles for delivery of an antimitotic agent to vascular smooth muscle cells
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DOI：
10.1016/s1054-8807(02)00165-5
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发表时间：
2003-03-01
影响因子：
3.7
通讯作者：
Keenan, AK
中科院分区：
文献类型：
--
作者：
Doorty, KB;Golubeva, TA;Keenan, AK
前言：局部应用抗分裂药物是一种潜在的治疗策略，可以保护受损的冠状动脉血管免受内膜增生和再狭窄的影响。本研究旨在建立热响应性聚(N-异丙基丙烯酰胺)共聚物膜可用于以受控方式将抗有丝分裂药物输送到血管平滑肌细胞(VSMC)的原理。方法：用N-异丙基丙烯酰胺(NiPAAm)和N-叔丁基丙烯酰胺(NtBAAm)的不同质量比(w/w)的N-异丙基丙烯酰胺(NiPAAm)和N-叔丁基丙烯酰胺(NtBAAm)在室温下负载抗有丝分裂药物秋水仙碱(100nmol/膜)，制备了一系列共聚物膜。结果：37℃时秋水仙碱的释放量与NtBAAm的量成反比，48h释放量分别为26、17和0.5nmol。在细胞毒性研究中，当与共聚物孵育24小时的培养液(在不含秋水仙素的情况下)进一步与靶向牛主动脉平滑肌细胞(BASMC)孵育时，细胞活力没有损失。从三种共聚物膜中释放的秋水仙素显著抑制BASMC的增殖和随机迁移：100 nM秋水仙碱(从65：35NiPAAm：NtBAAm释放)使细胞增殖减少到不含秋水仙素时的25.7+/-1.7%(对照组)，细胞随机迁移减少到对照组的37.7+/-5.7%(平均S.E.M.，n=3，P
Introduction: Local delivery of antimitotic agents is a potential therapeutic strategy for protection of injured coronary vasculature against intimal hyperplasia and restenosis. This study sought to establish the principle that thermoresponsive poly(N-isopropylacrylamide) co-polymer films can be used to deliver, in a controlled manner, an antimitotic agent to vascular smooth muscle cells (VSMC). Methods: A series of co-polymer films was prepared, using varying ratios (w/w) of N-isopropylacrylamide (NiPAAm) monomer to N-tert-butylacrylamide (NtBAAm) and loaded with the antimitotic agent colchicine (100 nmol/film) at room temperature. Results: The extent of colchicine release at 37 degreesC was inversely proportional to the amount of NtBAAm in co-polymer films: release after 48 h from 85:15, 65:35 and 50:50 (NiPAAm:NtBAAm) films was 26, 17 and 0.5 nmol, respectively. In cytotoxicity studies, when medium incubated with co-polymers for 24 h (in the absence of colchicine) was further incubated with target bovine aortic smooth muscle cells (BASMC), no loss of cell viability occurred. Colchicine released from all three co-polymer films significantly inhibited proliferation and random migration of BASMC: 100 nM colchicine (released from 65:35 NiPAAm:NtBAAm) reduced cell proliferation to 25.7 +/- 1.7% of levels seen in the absence of colchicine (control) and random cell migration to 37.7 +/- 5.7% of control (mean S.E.M., n=3, P