Temperature-triggered on-demand drug release enabled by hydrogen-bonded multilayers of block copolymer micelles.
Temperature-triggered on-demand drug release enabled by hydrogen-bonded multilayers of block copolymer micelles.
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DOI：
10.1016/j.jconrel.2013.06.031
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发表时间：
2013-10
期刊：
影响因子：
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通讯作者：
Zhichen Zhu;Ning Gao;Hongjun Wang;S. Sukhishvili
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文献类型：
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作者：
Zhichen Zhu;Ning Gao;Hongjun Wang;S. Sukhishvili
我们报告氢键层层（LBL）膜作为一个强大的，可重复使用的平台，温度触发的“按需”释放的药物。通过将单宁酸（TA）与温度响应性嵌段共聚物胶束（BCM）组装，使具有高载药量、温度控制的开关药物释放和在生理条件下的稳定性的膜成为可能，所述温度响应性嵌段共聚物胶束（BCM）是通过加热中性二嵌段共聚物聚乙烯的溶液而预形成的。（N-乙烯基吡咯烷酮）-b-聚（N-异丙基丙烯酰胺）（PVPON-b-PNIPAM）的混合物的温度升高至高于PNIPAM的下临界溶解温度（LCST）的温度。在生理条件下，所述PEG 4/TA膜表现出温度触发的溶胀/去溶胀转变（在37 °C和20 °C下的溶胀比分别为1.75和1.2）。将模型药物阿霉素（DOX）以高药物-基质比（~ 9.3wt.%）掺入膜中。DOX/膜质量），总负载能力由膜厚度控制。在37 °C下，DOX被有效地保留在PDX/TA膜的疏水性聚合物核内，而暴露于较低温度（20 °C）触发了DOX的快速释放。虽然裸的含BCM的膜和负载有DOX的膜在37 °C下都没有显示出细胞毒性，但在较低温度下从膜释放的药物表现出针对乳腺癌细胞的高效力。用1.5 μ m厚的DOX负载膜证明了重复的开/关药物释放，允许至少三个30分钟的冷却循环，在4天的时间内释放一致的DOX（每个循环释放约12-16%的负载DOX）。尽管存在与多次溶胀/去溶胀循环相关的显著应力，但膜在PBS中保持其结构完整性，并且每个膜可以重复加载药物并使用超过15次，膜厚度仅损失约7%，并且再加载能力或释放曲线没有明显变化。这项工作提出了第一个概念验证的效用的温度响应性的BCM含有膜的重复按需释放的药物。
We report on hydrogen-bonded layer-by-layer (LbL) films as a robust, reusable platform for temperature-triggered “on-demand” release of drugs. Films with high drug loading capacity, temperature-controlled on–off drug release, and stability at physiological conditions were enabled by assembly of tannic acid (TA) with temperature-responsive block copolymer micelles (BCMs), which were pre-formed by heating solutions of a neutral diblock copolymer, poly(N-vinylpyrrolidone)-b-poly(N-isopropylacrylamide) (PVPON-b-PNIPAM), to a temperature above the lower critical solution temperature (LCST) of PNIPAM. The BCM/TA films exhibited temperature-triggered swelling/deswelling transitions at physiological conditions (swelling ratios of 1.75 and 1.2 at 37 °C and 20 °C, respectively). A model drug, doxorubicin (DOX) was incorporated into the film at a high drug-to-matrix ratio (~ 9.3 wt.% of DOX per film mass), with a total loading capacity controlled by the film thickness. At 37 °C, DOX was efficiently retained within the hydrophobic BCM cores of BCM/TA films, whereas exposure to a lower temperature (20 °C) triggered fast DOX release. While neither bare BCM-containing films nor films loaded with DOX showed cytotoxicity at 37 °C, drug released from films at lower temperature exhibited high potency against breast cancer cells. Repeated on/off drug release was demonstrated with 1.5-μm-thick DOX-loaded films, allowing at least three 30-min cooling cycles with consistent DOX (~ 12–16% of loaded DOX released for each cycle) released over a 4-day period. Despite significant stress associated with multiple swelling/deswelling cycles, films maintained their structural integrity in PBS, and each film could be repeatedly loaded with drug and used more than 15 times with only ~ 7% loss in film thickness and no obvious changes in reloading capacity or release profiles. This work presents the first proof-of-concept utility of temperature-responsive BCM-containing films for repeated on-demand release of a drug.