Ye Lin, Liu Xiaoqiong, Ito Kohzo, Feng Zengguo
School of Materials Science and Engineering, Beijing Institute of Technology, No. 5 Zhongguancun South Road, Haidian, Beijing, 100081, China.
J Mater Chem B. 2014 Sep 21;2(35):5746-5757. doi: 10.1039/c4tb00719k. Epub 2014 Jul 28.
A polyrotaxane-containing triblock copolymer (PRTBP) was synthesized via ATRP of NIPPAAm initiated by the self-assembly of α-cyclodextrins (α-CDs) with distal 2-bromopropionyl end-capped poly(caprolactone) (Br-PCL-Br) in water at 25 °C. After that, an azobenzene group was introduced into the polyrotaxane block via the hydroxyl of threaded α-CD to get azo-substituted PRTBP (APRTBP). The structure was characterized in detail by H NMR, FTIR and WXRD techniques. Its thermal and light responsive properties were demonstrated by turbidity measurements and UV spectroscopy, respectively. Furthermore, micelles with diameters of around 100 nm were prepared from APRTBP in aqueous solution. Dynamic laser scattering (DLS) measurements demonstrated that the micelles contracted under UV irradiation and successively expanded under visible light, which offers a reversible on-off switch for controlling the drug release behavior of micelles. Consequently, the in vitro drug release curve, which is similar to the pharmacokinetic curve of multiple dosing administrations, was achieved when UV and visible light were applied alternatively to simulate on-off states for drug release. It also showed that the micelle possessed a significantly higher release rate and higher cumulative release amount under UV irradiation than those under visible light. Furthermore, the low critical solution temperature (LCST) of NIPPAAm blocks in APRTBP can be used as another switch to trigger the drug release as implied by in vitro drug release tests using doxorubicin (DOX) as the model drug. Considering its interesting dual stimuli-responsiveness and on-off switch-like behaviors resulting from dual responsiveness, APRTBP shows considerable potential as a candidate for controlled drug delivery systems and other possible biomedical applications.
通过α-环糊精（α-CD）与末端带有2-溴丙酰基的聚己内酯（Br-PCL-Br）在25℃的水中自组装引发NIPPAAm的原子转移自由基聚合（ATRP），合成了一种含聚轮烷的三嵌段共聚物（PRTBP）。之后，通过穿线的α-CD的羟基将偶氮苯基团引入聚轮烷嵌段，得到偶氮取代的PRTBP（APRTBP）。通过核磁共振氢谱（1H NMR）、傅里叶变换红外光谱（FTIR）和广角X射线衍射（WXRD）技术对其结构进行了详细表征。分别通过浊度测量和紫外光谱证明了其热响应和光响应性能。此外，在水溶液中由APRTBP制备了直径约为100nm的胶束。动态激光散射（DLS）测量表明，胶束在紫外光照射下收缩，在可见光下相继膨胀，这为控制胶束的药物释放行为提供了一个可逆的开关。因此，当交替施加紫外光和可见光以模拟药物释放的开关状态时，获得了与多次给药的药代动力学曲线相似的体外药物释放曲线。结果还表明，胶束在紫外光照射下的释放速率和累积释放量明显高于可见光照射下的。此外，如以阿霉素（DOX）为模型药物的体外药物释放试验所示，APRTBP中NIPPAAm嵌段的低临界溶液温度（LCST）可作为另一个触发药物释放的开关。考虑到其有趣的双重刺激响应性以及由双重响应性产生的类似开关的行为，APRTBP作为可控药物递送系统和其他可能的生物医学应用的候选物具有相当大的潜力。
