Inner core segment design for drug delivery control of thermo-responsive polymeric micelles
Inner core segment design for drug delivery control of thermo-responsive polymeric micelles
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DOI：
10.1016/s0168-3659(99)00242-4
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发表时间：
2000-03-01
影响因子：
10.8
通讯作者：
Okano, T
中科院分区：
文献类型：
--
作者：
Chung, JE;Yokoyama, M;Okano, T
使用胶束内核和外部尖锐聚合物化学物质的组合，研究了针对特定药物递送功能的聚合物胶束热响应行为的修改。采用由PIPAAm（聚（N-异丙基丙烯酰胺））与PBMA（聚（甲基丙烯酸丁酯））或PSt（聚苯乙烯）的AB嵌段共聚物组成的聚合物胶束。 PIPAAm-PBMA和PIPAAm-PSt嵌段共聚物在20℃下在有机溶剂中对水透析布洛赫共聚物溶液后形成核壳胶束结构。通过透析将疏水性药物阿霉素(ADR)加载到聚合物胶束的内核中。通过 DLS（动态光散射）和透射率测量观察到，聚合物表现出可逆的胶束间分散/聚集，以响应通过聚合物外壳较低临界溶液温度（PIPAAm 的 LCST = 32.5 摄氏度）的温度循环。在 LCST 附近加热时，PIPAAm-PBMA 胶束分别表现出芘和 1,3-双(1-芘基)丙烷 (PC3P) 感觉到的微极性突然增加和微刚性突然下降。相比之下，在 20 至 40 摄氏度的温度范围内，PIPAAm-PSt 胶束比 PIPAAm-PBMA 胶束保持恒定值，具有更低的微极性和更高的微刚性。根据这些结果，通过 LCST 的温度循环，外壳聚合物结构变化所产生的结构变形被认为，PBMA 核具有比外壳 PIPAAm LCST 更低的 T-g（约 20 摄氏度）。具有比外壳 LCST 高得多的 Tf（约 100 摄氏度）的 PSt con 保留其结构，无论外壳如何变化。 PIPAAm-PBMA micelles released ADR only when heated above the LCST, while PIPAAm-PSt micelles did not.当加热至高于 LCST 时，用负载 ADR 的 PIPAAm-PBMA 胶束处理的细胞培养物显示出高体外细胞毒性，而负载 ADR 的 PIPAAm-PSt 胶束处理的细胞培养物表现出非常低的体外细胞毒性，无论通过 LCST 的温度如何变化。构成胶束内核的疏水性片段的性质为热响应性药物释放和热响应性聚合物胶束的药物活性提供了重要的控制点。 (C) 2000 Elsevier Science B.V. 保留所有权利。
Modification of the thermo-responsive behavior of polymeric micelles for specific drug delivery functions was investigated using combinations of micellar inner cores and outer shrill polymer chemistries. Polymeric micelles comprised of AB block copolymers of PIPAAm (poly(N-isopropylacrylamide)) with either PBMA (poly(butyl methacrylate)) or PSt (polystyrene) were employed. PIPAAm-PBMA and PIPAAm-PSt block copolymers formed a core-shell micellar structure after dialysis of the bloch copolymer solutions in organic solvents against water at 20 degrees C. The hydrophobic drug, adriamycin, (ADR) was loaded into the inner core of the polymeric micelles by dialysis. The polymers showed reversible intermicellar dispersion/aggregation in response to temperature cycles through an outer polymer shell lower critical solution temperature (LCST for PIPAAm=32.5 degrees C), observed by DLS (dynamic light scattering) and transmittance measurements. Upon heating about the LCST, PIPAAm-PBMA micelles exhibited an abrupt increase in micropolarity and an abrupt decrease in microrigdity sensed by pyrene and 1,3-bis(1-pyrenyl)propane (PC3P), respectively. In contrast, PIPAAm-PSt micelles maintained constant values with lower micropolarity and higher microrigidity than those of PIPAAm-PBMA micelles: over the temperature range 20 to 40 degrees C. From these results, structural deformations produced by outer shell polymer structural change with temperature cycles through the LCST are proposed fur the PBMA core possessing a lower T-g (ca. 20 degrees C) than the outer shell PIPAAm LCST. The PSt con with a much higher Tf (ca. 100 degrees C) than the outer shell LCST retained its: structure, regardless of outer shell changes. PIPAAm-PBMA micelles released ADR only when heated above the LCST, while PIPAAm-PSt micelles did not. Cell cultures treated with PIPAAm-PBMA micelles loaded with ADR showed high in vitro cytotoxicity when heated above the LCST, while PIPAAm-PSt micelles: loaded with ADR expressed very low in vitro cytotoxicity irrespective of temperature change through the LCST. The nature of hydrophobic segments comprising the micelle inner core offers an important control point for thermo-responsive drug release and the drug activity of the thermo-responsive polymeric micelle. (C) 2000 Elsevier Science B.V. All rights reserved.