复合负载姜黄素-纳米新剂型抑制肝癌细胞增殖的机理研究

Hepatocellular carcinoma is a serious threat to human, but lack enough and effective curative substance. Therefore, it is of great importance to search for new agents or develop new use for old drugs. Curcumin, a natural plant-based product, has shown signi?cant promise against cancer. But its clinical development has been limited due to its fast metabolism and poor water solubility. So it is necessary to develope the new dosage form to improve its drawbacks. Our previous studies have showed that curcumin-SLNs could inhibit the proliferation of SMMC-7721 cells in a dose-and time-dependent manner. And the pharmacokinetic properties of free curcumin were improved by 30 folds when it was encapsulated in nanoparticles.In order to find a suitale drug carrier for curcumin, the morphology, release properties, tissue distribution and other aspects of this new agent were characterized.Through cell experiments and animal experiments, we want to observe its therapeutic effect to treatment mechanism, and check the best administration time, dosage and dosing method for curcumin. This new agent for the treatment of hepatocellular carcinoma could give a new way in old drug in treatment.

肝癌严重威胁着人类的健康，缺乏有效安全的治疗药物，急需新药研发或老药新用，而实验中姜黄素（Curcumin）单方中药可以显著提高肝癌治疗效果。姜黄素为天然植物药物，虽然已研究证明其对肿瘤有较好的治疗效果，但存在水溶性差，生物利用度低的缺点，急需从剂型上进行改进。课题组的前期研究结果表明姜黄素纳米新剂型在体外能够抑制肝癌细胞SMMC-7721的生长，姜黄素纳米新剂型可将小鼠体内血药浓度提高至原来的30倍，提示姜黄素纳米颗粒具有很强的抗肝癌应用前景。因此，本课题拟在前期研究基础上，优化姜黄素载体的配方及其制备方法，并对新剂型的形貌、释放性能及组织分布等方面进行检测，获得最佳新剂型；通过体外细胞实验和在体动物实验等观察其对肝癌的治疗效果及治疗机理，并确定最佳给药时间、给药剂量及给药方法，为姜黄素新剂型在肝癌治疗上的老药新用提供理论指导。

肝癌严重威胁着人类的健康，缺乏有效安全的治疗药物，急需新药研发或老药新用，而实验中姜黄素单方中药可以显著提高肝癌治疗效果。姜黄素为天然植物药物，虽然已研究证明其对肿瘤有较好的治疗效果，但存在水溶性差，生物利用度低的缺点，急需从剂型上进行改进。课题组利用SLN和LDH纳米材料改善姜黄素剂型，并对其进行详细表针，各项数据显示合成的纳米姜黄素粒子符合前期实验期望，可用于姜黄素抗肿瘤的进一步研究，接着进一步实验证实纳米姜黄素的抗肿瘤效应明显优于单纯姜黄素，主要体现在更强的促凋亡效应上。同时随着经典化疗药物的广泛开展，肿瘤多药耐药已经成为肿瘤病人化学药物治疗的巨大障碍，文献报道显示，化疗药物与姜黄素联合能够有效逆转肿瘤多耐药多种化疗药物。课题组制备了结构良好、生物安全的姜黄素混合纳米药物，实现氟尿嘧啶和姜黄素共载，新的纳米药物在体内、体外均展现处良好抑制肝癌氟尿嘧啶耐药细胞，为肝癌抗肿瘤耐药药物的研发提供新思路。