Zhang Jian, Qian Zhiyu, Gu Yueqing
Department of Biomedical Engineering, School of Life Science and Technology, China Pharmaceutical University, Tongjia Lane No. 24, Nanjing 210009, People's Republic of China.
Nanotechnology. 2009 Aug 12;20(32):325102. doi: 10.1088/0957-4484/20/32/325102. Epub 2009 Jul 21.
Thermally responsive poly(N-isopropylacrylamide-co-acrylamide) (P(NIPA-co-AAm)) nanohydrogel (NHG) with a diameter of about 50 nm and a lower critical solution temperature (LCST) of about 40 degrees C was synthesized by a previously reported precipitation polymerization method. The physical properties including LCST, diameter and morphology were characterized. Four hydrophobic model drugs (5-fluorouracil (5-FU), fluorescein, docetaxel (DTX) and near-infrared dye-12 (NIRD-12)) with different hydrophilicities were respectively entrapped into the nanoparticles and their in vitro release kinetics from NHG was investigated. DTX was ultimately chosen as the goal anti-tumor drug and optimally entrapped into NHG with a drug loading content (DLC) of 7.38% and encapsulation efficiency (EE) of 73.8%. An in vitro drug release test indicated that DTX-loaded NHG had zero-order release kinetics at 43 degrees C. The respective anti-tumor efficacy of DTX-loaded NHG with or without hyperthermia on tumor tissue was evaluated in Kunming mice-bearing S180 sarcoma. The inhibition rates of DTX-loaded NHG with or without hyperthermia were 78.15% and 48.78%, respectively. DTX-loaded NHG also showed much lower toxicity during the therapeutic procedure. Results indicated that this kind of thermally responsive, drug-loaded NHG could be used as a promising strategy for tumor therapy with the help of local hyperthermia treatment.
采用先前报道的沉淀聚合法合成了直径约50 nm、低临界溶液温度（LCST）约为40℃的热响应性聚（N-异丙基丙烯酰胺-共-丙烯酰胺）（P（NIPA-共-AAm））纳米水凝胶（NHG）。对其包括LCST、直径和形态在内的物理性质进行了表征。将四种具有不同亲水性的疏水性模型药物（5-氟尿嘧啶（5-FU）、荧光素、多西他赛（DTX）和近红外染料-12（NIRD-12））分别包封到纳米颗粒中，并研究了它们从NHG的体外释放动力学。最终选择DTX作为目标抗肿瘤药物，并以7.38%的载药量（DLC）和73.8%的包封率（EE）最佳地包封到NHG中。体外药物释放试验表明，载DTX的NHG在43℃下具有零级释放动力学。在荷S180肉瘤的昆明小鼠中评估了载DTX的NHG在有或无热疗情况下对肿瘤组织的各自抗肿瘤疗效。载DTX的NHG在有或无热疗情况下的抑制率分别为78.15%和48.78%。载DTX的NHG在治疗过程中也显示出低得多的毒性。结果表明，这种热响应性、载药的NHG在局部热疗的帮助下可作为一种有前景的肿瘤治疗策略。
