Metal-organic framework IRMOFs coated with a temperaturesensitive gel delivering norcantharidin to treat liver cancer

BACKGROUND Norcantharidin(NCTD)is suitable for the treatment of primary liver cancer,especially early and middle primary liver cancer.This compound can reduce tumors and improve immune function.However,the side effects of NCTD have limited its application.There is a marked need to reduce the side effects and increase the efficacy of NCTD.AIM To develop a nanomaterial carrier,NCTD-loaded metal-organic framework IRMOF-3 coated with a temperature-sensitive gel(NCTD-IRMOF-3-Gel),aiming to improve the anticancer activity of NCTD and reduce the drug dose.METHODS NCTD-IRMOF-3-Gel was obtained by a coordination reaction.The apparent characteristics and in vitro release of NCTD-IRMOF-3-Gel were investigated.Cell cytotoxicity assays,flow cytometry,and apoptosis experiments in mouse hepatoma(Hepa1-6)cells were used to determine the anti-liver cancer activity of NCTD-IRMOF-3-Gel in in vitro models.RESULTS The particle size of NCTD-IRMOF-3-Gel was 50-100 nm,and the particle size distribution was uniform.The release curve showed that NCTD-IRMOF-3-Gel had an obvious sustained-release effect.The cytotoxicity assays showed that the free drug NCTD and NCTD-IRMOF-3-Gel treatments markedly inhibited Hepa1-6 cell proliferation,and the inhibition rate increased with increasing drug concentration.By flow cytometry,NCTD-IRMOF-3-Gel was observed to block the Hepa1-6 cell cycle in the S and G2/M phases,and the thermosensitive gel nanoparticles may inhibit cell proliferation by inducing cell cycle arrest.Apoptosis experiments showed that NCTD-IRMOF-3-Gel induced the apoptosis of Hepa1-6 cells.CONCLUSION Our results indicated that the NCTD-IRMOF-3-Gel may be beneficial for liver cancer disease treatment.

Effect of peritumoral injection of boanmycin hydrochloride within temperature-sensitive in situ gel using Hep-G2 hepatoma nude mice model

Background Boanmycin hydrochloride, a new antitumor agent, has a short half-life and fast clearance speed in vivo. The aim of this research was to investigate the effectiveness of peritumor injection of boanmycin hydrochloride within temperature-sensitive gel in situ using Hep-G2 hepatoma nude mice model. Methods Nude mice with human Hep-G2 tumor in right flank were randomly divided into four groups： normal saline group, in situ gel only group, boanmycin hydrochloride in situ saline group, and boanmycin hydrochloride in situ gel group, and were treated with injection of corresponding agents into peripheral tissue of the tumor. The volume of the tumor and the body weight of the mice were regularly measured, and tumor growth curve was generated. The size, internal echo, and blood flow of the tumors were observed by color Doppler ultrasonography. Histopathologic changes of the tumor after treatment were observed under both optical and transmission electron microscopy. Results The tumor growth was significantly inhibited by peritumoral therapy in boanmycin hydrochloride in situ gel group with the tumor inhibitory rate of 86.76%. The blood flow of the tumor was still seen in both normal saline group and in situ gel only group on color Doppler ultrasound. Punctate calcification and dotted blood flow were seen in boanmycin hydrochloride group; however, there was massive calcification and no blood flow in the tumor in the boanmycin hydrochlodde in situ gel group. Large areas of necrosis and apoptotic cells were shown by microscopic observation in boanmycin hydrochloride in situ gel group. Conclusion Temperature-sensitive boanmycin hydrochloride in situ gel can effectively delay the release of boanmycin hydrochloride and increase its anticancer effects for liver cancer in animal model.

氯麻鼻用凝胶剂的制备和质量控制

目的开发一种含有氯雷他定和麻黄碱的复方鼻腔给药新制剂。方法以卡波姆为辅料,制备了氯麻鼻用凝胶剂;同时采用HPLC进行氯雷他定和麻黄碱的含量测定。结果氯雷他定、麻黄碱的平均回收率分别为100.17%、99.99%;RSD分别为0.62%、0.67%。结论该制剂处方合理、工艺简单、质量可控,适用于医院制剂。

瑞利敏凝胶喷鼻剂的制备和临床应用

目的:制备瑞利敏凝胶喷鼻剂并观察其临床疗效。方法:以聚羧乙烯为辅料,制备瑞利敏凝胶喷鼻剂并建立质量控制方法,观察临床疗效。结果:制备工艺简单,临床疗效可靠。结论:该制剂可用于临床。

氯雷他定温敏型鼻用凝胶的制备及质量研究

目的制备氯雷他定温敏型鼻用凝胶并考察其质量。方法采用包合技术制备氯雷他定和羟丙基-β-环糊精包合物,再与不同配方的泊洛沙姆、卡波姆制成温敏型鼻用凝胶,考察凝胶的胶凝温度、胶凝时间和黏附力等指标,优选基质处方。结果制备得到的包合物载药量为20.15%,包合率为82.07%,鼻用凝胶基质为190 g·L-1泊洛沙姆407和1.0 g·L-1卡波姆,其胶凝温度为32.4℃,黏附力61.5 g·cm-2。结论本方法选定的包合物和基质处方适用于氯雷他定温敏型鼻用凝胶的制备。

葡聚糖凝胶微柱-HPLC测定氯雷他定二元醇质体包封率

目的：建立氯雷他定二元醇质体包封率的测定方法。方法：采用凝胶微柱离心法分离游离药物与二元醇质体,以HPLC测定氯雷他定的药物含量,计算二元醇质体的包封率。结果：氯雷他定浓度在10.2~102.0μg·ml-1内线性关系良好（r=0.999 5）。3批次氯雷他定二元醇质体的包封率分别为86.75%,87.26%,86.00%。结论：该方法简便、迅速,可准确测定氯雷他定二元醇质体的包封率。

氯雷他定温敏性凝胶鼻粘膜毒性以及刺激性探究

探究氯雷他定温敏性凝胶剂通过鼻腔给药是否产生鼻黏膜毒性以及刺激性。以鸡胚尿囊膜为模型进行空白凝胶以及给药凝胶对比试验,观察是否产生出血、凝血、溶血等现象;以新西兰白兔为模型观察凝胶剂的刺激性,观察是否出现皮肤红斑、水肿等情况。结果表明,氯雷他定凝胶剂对鸡胚尿囊膜未产生出血、凝血、溶血现象;也不会引起对新西兰白兔刺激反应。