Xu Na, Huang Xiaobei, Yin Guangfu, Bu Meijiao, Pu Ximing, Chen Xianchun, Liao Xiaoming, Huang Zhongbing
College of Materials Science & Engineering, Sichuan University Chengdu 610065 China
RSC Adv. 2018 Apr 25;8(28):15604-15612. doi: 10.1039/c8ra02117a. eCollection 2018 Apr 23.
In contrast with traditional chemotherapy, controlled drug delivery systems provide many advantages. Herein, a thermosensitive star polymer pompon with a core-arm structure was synthesized using a grafting-on method as a thermo-responsive controlled release drug carrier. Single-chain cyclized/knotted poly tetra(ethylene glycol) diacrylate (polyTEGDA) was used as the hydrophobic core, and thermosensitive linear poly(-isopropylacrylamide--methylolacrylamide) (poly(NIPAM--NMA)) was selected as the hydrophilic arm. Below or above its lower critical solution temperature (LCST), the linear poly(NIPAM--NMA) grafted onto the polyTEGDA core adopted a stretched or curled status, respectively, then the drug could be loaded in or extruded out. The LCST of star polyTEGDA--poly(NIPAM--NMA) was adjusted to slightly above body temperature (37 °C). The antitumor drug doxorubicin (DOX) was successfully loaded into the pompons with a high loading capacity of 19.45%. The cumulative release of DOX from loaded pompons for 72 hours was 71% and 20.7% at 42 °C and 37 °C, respectively, indicating that the excellent temperature-controlled release characteristics result from the unique thermo-responsive extrusion effect. Moreover, DOX loaded polyTEGDA--poly(NIPAM--NMA) pompons achieved better antitumor ability against ovarian carcinoma SKOV3 cells at 42 °C compared with that at 37 °C. These results suggest that star polyTEGDA--poly(NIPAM--NMA) pompons have considerable promise as thermo-responsive controlled drug delivery carriers.
与传统化疗相比,控释给药系统具有许多优势。在此,采用接枝法合成了一种具有核-臂结构的热敏性星形聚合物绒球,作为热响应控释药物载体。单链环化/打结的聚四乙二醇二丙烯酸酯(聚TEGDA)用作疏水核,热敏性线性聚(N-异丙基丙烯酰胺-N-羟甲基丙烯酰胺)(聚(NIPAM-NMA))被选作亲水臂。在其低临界溶液温度(LCST)以下或以上,接枝到聚TEGDA核上的线性聚(NIPAM-NMA)分别呈现伸展或卷曲状态,然后药物可以被载入或挤出。星形聚TEGDA-聚(NIPAM-NMA)的LCST被调节至略高于体温(37℃)。抗肿瘤药物阿霉素(DOX)以19.45%的高载药量成功载入绒球中。载药绒球中DOX在42℃和37℃下72小时的累积释放率分别为71%和20.7%,表明优异的温度控释特性源于独特的热响应挤出效应。此外,与37℃相比,载有DOX的聚TEGDA-聚(NIPAM-NMA)绒球在42℃时对卵巢癌SKOV3细胞具有更好的抗肿瘤能力。这些结果表明,星形聚TEGDA-聚(NIPAM-NMA)绒球作为热响应控释药物载体具有很大的潜力。