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Injectable Thermoresponsive Hydrogel Formed by Alginate-g-Poly(N-isopropylacrylamide) That Releases Doxorubicin-Encapsulated Micelles as a Smart Drug Delivery System
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2017-10-02 00:00:00 , DOI: 10.1021/acsami.7b12849 Min Liu 1, 2 , Xia Song 1 , Yuting Wen 1 , Jing-Ling Zhu 1 , Jun Li 1, 2
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2017-10-02 00:00:00 , DOI: 10.1021/acsami.7b12849 Min Liu 1, 2 , Xia Song 1 , Yuting Wen 1 , Jing-Ling Zhu 1 , Jun Li 1, 2
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In this work, we have synthesized a thermoresponsive copolymer, alginate-g-poly(N-isopropylacrylamide) (alginate-g-PNIPAAm) by conjugating PNIPAAm to alginate, where PNIPAAm with different molecular weights and narrow molecular weight distribution was synthesized by atomic transfer radical polymerization. The copolymer dissolved in water or phosphate-buffered saline buffer solution at room temperature and formed self-assembled micelles with low critical micellization concentrations when the temperature increased to above their critical micellization temperatures. At higher concentration, that is, 7.4 wt % in water, the copolymer formed solutions at 25 °C and turned into thermosensitive hydrogels when temperature increased to the body temperature (37 °C). Herein, we hypothesized that the thermoresponsive hydrogels could produce self-assembled micelles with the dissolution of the alginate-g-PNIPAAm hydrogels in a biological fluid or drug release medium. If the drug was hydrophobic, the hydrogel eventually could release and produce drug-encapsulated micelles. In our experiments, we loaded the anticancer drug doxorubicin (DOX) into the alginate-g-PNIPAAm hydrogels and demonstrated that the hydrogels released DOX-encapsulated micelles in a sustained manner. The slowly released DOX-loaded micelles enhanced the cellular uptake of DOX in multidrug resistant AT3B-1 cells, showing the effect of overcoming the drug resistance and achieving better efficiency for killing the cancer cells. Therefore, the injectable thermoresponsive hydrogels formed by alginate-g-PNIPAAm and loaded with DOX turned into a smart drug delivery system, releasing DOX-encapsulated micelles in a sustained manner, showing great potential for overcoming the drug resistance in cancer therapy.
中文翻译：
由藻酸盐-g-聚（N-异丙基丙烯酰胺）形成的可注射热敏水凝胶，将阿霉素包裹的胶束释放为智能药物递送系统
在这项工作中，我们合成了一种热响应性共聚物，藻酸盐-g-聚（N-异丙基丙烯酰胺）（藻酸盐-g-PNIPAAm），将PNIPAAm与藻酸盐结合，通过原子转移自由基聚合合成分子量不同，分子量分布窄的PNIPAAm。共聚物在室温下溶解于水或磷酸盐缓冲的盐缓冲溶液中，并且当温度升高至高于其临界胶束化温度时，形成具有低临界胶束化浓度的自组装胶束。在较高浓度下，即在水中为7.4 wt％时，该共聚物在25°C时形成溶液，并在温度升高至体温（37°C）时变成热敏性水凝胶。在此，我们推测，温敏凝胶可产生自组装胶束与藻酸盐的溶解摹-PNIPAAm水凝胶在生物流体或药物释放介质中。如果药物是疏水的，则水凝胶最终会释放并产生药物包裹的胶束。在我们的实验中，我们将抗癌药阿霉素（DOX）加载到藻酸盐-g -PNIPAAm水凝胶中，并证明该水凝胶以持续的方式释放DOX包裹的胶束。缓慢释放的载有DOX的胶束增强了多药耐药AT3B-1细胞对DOX的细胞吸收，显示出克服耐药性的效果，并具有更好的杀死癌细胞的效率。因此，可注射的水凝胶温敏由藻酸盐形成克-装有DOX的-PNIPAAm变成了智能药物输送系统，可以持续释放DOX封装的胶束，在克服癌症治疗的耐药性方面显示出巨大的潜力。
更新日期：2017-10-02
中文翻译：
由藻酸盐-g-聚（N-异丙基丙烯酰胺）形成的可注射热敏水凝胶，将阿霉素包裹的胶束释放为智能药物递送系统
在这项工作中，我们合成了一种热响应性共聚物，藻酸盐-g-聚（N-异丙基丙烯酰胺）（藻酸盐-g-PNIPAAm），将PNIPAAm与藻酸盐结合，通过原子转移自由基聚合合成分子量不同，分子量分布窄的PNIPAAm。共聚物在室温下溶解于水或磷酸盐缓冲的盐缓冲溶液中，并且当温度升高至高于其临界胶束化温度时，形成具有低临界胶束化浓度的自组装胶束。在较高浓度下，即在水中为7.4 wt％时，该共聚物在25°C时形成溶液，并在温度升高至体温（37°C）时变成热敏性水凝胶。在此，我们推测，温敏凝胶可产生自组装胶束与藻酸盐的溶解摹-PNIPAAm水凝胶在生物流体或药物释放介质中。如果药物是疏水的，则水凝胶最终会释放并产生药物包裹的胶束。在我们的实验中，我们将抗癌药阿霉素（DOX）加载到藻酸盐-g -PNIPAAm水凝胶中，并证明该水凝胶以持续的方式释放DOX包裹的胶束。缓慢释放的载有DOX的胶束增强了多药耐药AT3B-1细胞对DOX的细胞吸收，显示出克服耐药性的效果，并具有更好的杀死癌细胞的效率。因此，可注射的水凝胶温敏由藻酸盐形成克-装有DOX的-PNIPAAm变成了智能药物输送系统，可以持续释放DOX封装的胶束，在克服癌症治疗的耐药性方面显示出巨大的潜力。
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