目的 设计具有不同相变速度的纳米凝胶(nanogel),筛选可用于经导管动脉化疗栓塞(TACE)的栓塞和载药材料。方法 通过乳液聚合制备N-异丙基丙烯酰胺(NIPAM)-丙烯酸(AA)分别为3∶1、2∶1和1∶1的无规共聚纳米凝胶P(NIPAM-Co-AA)(PNA)和互穿网络纳米凝胶PNA-IPN,并对其颗粒的形貌、温敏性、溶液的相变行为、流变学性质进行表征,评价各nanogel的栓塞及载药性能。结果 nanogel为较为均一的近似球体,PNA的粒径为386~795 nm,PNA-IPN的粒径为367~750 nm;温度升高可使凝胶的粒径减小,AA比例增加会导致凝胶的温敏性降低、相变温度升高、凝胶速度加快但凝胶强度降低。与PNA相比,PNA-IPN具有较小的粒径、较低的凝胶温度,较快的凝胶速度和较高的凝胶强度。PNA-IPN-2可通过静电吸附负载阿霉素,载药量为10.3%。结论 140 mg·mL-1的PNA-IPN-2溶液的凝胶温度、速度和强度适中,其“剪切变稀”的性质和药物释放特性对用于TACE十分有利,有望用作TACE中的纳米凝胶栓塞、载药材料。
Abstract
OBJECTIVE To design nanogels with different phase transition speeds and screen embolization and drug delivery materials that can be used for transcatheter arterial chemoembolization (TACE). METHODS Random copolymer PNA nanogels and interpenetrating polymer PNA-IPN nanogels, in which the ratio of co-monomers between N-isopropylacrylamide (NIPAM) and acrylic acid (AA) were 3∶1, 2∶1 and 1∶1, respectively, were prepared by emulsion polymerization. The embolization and drug-loaded capacities of nanogels were evaluated by characterization of their particle morphology, temperature sensitivity, solution phase transition behavior and rheological properties. RESULTS Nanogel particles were relatively uniform spheres. The particle size of PNA was 386-795 nm, and the particle size of PNA-IPN was 367-750 nm. The increase of temperature led to the decrease of particle size, while the increase of the ratio of the co-monomer AA caused the decrease of temperature sensitivity and gel strength of nanogels, and the increase of the phase transition temperature and the gelation speed. Compared with PNA, PNA-IPN-2 had slightly smaller particle size, lower gelation temperature, faster gelation speed and significantly increased gel strength. The PNA-IPN-2 could load doxorubicin by charge action with 10.3% of loading efficiency. CONCLUSION The 140 mg·mL-1 PNA-IPN-2 solution has suitable gelation temperature, gelation speed and gel strength. The shearthinning nature and drug release feature are very favorable for TACE, so the PNA-IPN-2 solution is promising for the applications in TACE as nanogels embolization and drug delivery materials.
关键词
纳米凝胶 /
互穿网络 /
凝胶速度 /
凝胶强度 /
栓塞
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Key words
nanogel /
interpenetrating polymer network /
gelation speed /
gel strength /
embolization
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中图分类号：
R944
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参考文献
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脚注
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基金
武汉市卫生和计划生育委员会科研项目资助(WX16C27)
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