微管蛋白的分离鉴定及其在抗癌药物筛选中的应用

用两个循环聚合——解聚的方法,从猪脑分离到部分纯化的微管蛋白,在聚丙烯酰胺凝胶电泳图谱上显示两个主峰带,即。微管蛋白(M:W.58,000)和β微管蛋白(M.W.54,000)。在ATP或GTP存在的MES缓冲液中37℃保温b微管蛋白迅速聚合为微管,A 350呈典型S形聚合曲线。在电子显微镜下显示网状微管结构。抗癌药物筛选实验表明:秋水仙碱明显抑制微管聚合;长春新碱低浓度(0.75-6μM)抑制微管蛋白聚合,高浓度(>6μM)时导致微管蛋白聚集(Aggregation),且在低温下不解聚。三尖杉酯类生物碱对微管蛋白的聚合及解聚未显示明显的影响。     

Rapidly separating dissolving microneedles with sustained-release colchicine and stabilized uricase for simplified long-term gout management

Despite growing prevalence and incidence, the management of gout remains suboptimal. The intermittent nature of the gout makes the long-term urate-lowering therapy (ULT) particularly important for gout management. However, patients are reluctant to take medication day after day to manage incurable occasional gout flares, and suffer from possible long-term toxicity. Therefore, a safe and easy-to-operate drug delivery system with simple preparation for the long-term management of gout is very necessary. Here, a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal. This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention. Furthermore, its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models. Besides, the drug co-delivery system could help avoid long-term daily oral colchicine, a drug with a narrow therapeutic index. This system also avoids mass injection of uricase by improving its stability, enhancing the clinical application value of uricase. In general, this two-drug system reduces the dosage of uricase and colchicine and improves the patient's compliance, which has a strong clinical translation.