Extended delivery of the antimitotic agent colchicine from thermoresponsive N-isopropylacrylamide-based copolymer films to human vascular smooth muscle cells.
Extended delivery of the antimitotic agent colchicine from thermoresponsive N-isopropylacrylamide-based copolymer films to human vascular smooth muscle cells.
复制标题
将抗有丝分裂剂秋水仙碱从热响应性 N-异丙基丙烯酰胺基共聚物膜延长递送至人血管平滑肌细胞。
DOI：
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
A. Keenan
中科院分区：
文献类型：
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作者：
S. J. Wilson;A. Gorelov;Y. Rochev;F. McGillicuddy;K. Dawson;W. Gallagher;A. Keenan
本研究的目的是建立温敏性聚（N-异丙基丙烯酰胺）共聚物膜的能力，提供生物活性浓度的抗有丝分裂剂的人血管平滑肌细胞（HASMC）在一段较长的时间。使用50：50（w/w）比例的N-异丙基丙烯酰胺（NiPAAm）单体与更疏水的N-叔丁基丙烯酰胺（NtBAAm）制备共聚物膜，并在室温下加载抗有丝分裂剂秋水仙碱（0.1微摩尔/膜）。秋水仙碱释放从电影持续超过14天的时间。在加载后24小时，覆盖膜的培养基中秋水仙碱的浓度为2.12 +/- 0.16 μ M;在7天时降至0.20 +/- 0.01 μ M，14天后进一步降至0.12 +/- 0.01 μ M。当随后置于HASMC上时，从共聚物膜释放的秋水仙碱抑制增殖：在0.1 μ M下，释放的秋水仙碱将增殖降低至对照细胞的18.5 +/-0.8%（p < 0.001，n = 9）。释放的秋水仙碱的抗增殖作用与天然秋水仙碱的抗增殖作用相当，如在单独的实验中观察到的。此外，从50：50聚合物膜释放的秋水仙碱抑制在与共聚物相同的环境中生长的细胞的增殖。细胞增殖的抑制不是由于共聚物中细胞毒性颗粒的释放，因为与共聚物一起孵育5天然后应用于HASMC的培养基没有改变细胞活力。总之，本研究表明，50：50 NiPAAm：NtBAAm共聚物可以在延长的时间段内将生物活性浓度的抗有丝分裂剂秋水仙碱递送至人血管细胞。
The aim of this study was to establish the capacity of thermoresponsive poly(N-isopropylacrylamide) copolymer films to deliver bioactive concentrations of an antimitotic agent to human vascular smooth muscle cells (HASMC) over an extended period of time. Copolymer films were prepared using a 50:50 (w/w) ratio of N-isopropylacrylamide (NiPAAm) monomer to the more hydrophobic N-tert-butylacrylamide (NtBAAm) and loaded with the antimitotic agent colchicine (0.1 micromol per film) at room temperature. Colchicine release from films was sustained over a 14-day period. At 24 h postloading, the concentration of colchicine in the medium overlying films was 2.12 +/- 0.16 microM; this fell to 0.20 +/- 0.01 microM at 7 days and decreased further to 0.12 +/- 0.01 microM after 14 days. Colchicine released from copolymer films inhibited proliferation when subsequently placed on HASMC: at 0.1 microM, released colchicine reduced proliferation to 18.5 +/- 0.8% of control cells (p < 0.001, n = 9). The antiproliferative effect of released colchicine was comparable to that of native colchicine, as observed in separate experiments. Furthermore, colchicine released from 50:50 polymer films inhibited the proliferation of cells grown in the same environment as the copolymer. Inhibition of cell proliferation was not due to the release of cytotoxic particles from the copolymer because medium incubated with copolymer for 5 days and then applied to HASMC did not alter cell viability. In conclusion, this study demonstrates that 50:50 NiPAAm:NtBAAm copolymers can deliver bioactive concentrations of the antimitotic agent colchicine to human vascular cells over an extended period of time.