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41.
目的 优化线粒体靶向金丝桃苷脂质体(DLD/Hyp-Lip)制备的最佳处方,并研究研究其在胎牛血清中的稳定性及体外释放行为,考察其线粒体靶向性。方法 采用薄膜分散法制备DLD/Hyp-Lip,以包封率和载药量为考察指标进行单因素实验,考察磷脂总量与金丝桃苷(hyperoside,Hyp)用量比、二硬脂酰磷脂酰乙醇胺-聚乙二醇(DSPE-PEG)与DLD用量比等条件对DLD/Hyp-Lip的影响,结合星点设计-效应面法优化DLD/Hyp-Lip处方。使用透射电子显微镜和粒径仪观察测定脂质体粒子外观、平均粒径和Zeta电位,采用血清稳定性实验和体外释药、线粒体靶向性对该载药系统进行评价。结果 DLD/Hyp-Lip最佳处方为磷脂总量和金丝桃苷用量比为12.50:1,磷脂总量与胆固醇用量比为6.00:1,DSPE-PEG与DLD用量比为3:5;测得金丝桃苷包封率为(95.57±0.56)%,载药量为(8.55±0.57)%。所制备的DLD/Hyp-Lip外观良好,平均粒径为(124.9±3.4)nm,Zeta电位为(-6.2±1.9)mV;在胎牛血清中性状稳定,在体外释放介质中24 h累积释放量达到40%。线粒体靶向实验表明DLD/Hyp-Lip可以促进药物聚集在线粒体部位。结论 采用此方法能够精准有效的优化DLD/Hyp-Lip的制备工艺,该方法操作简单方便,可以用于DLD/Hyp-Lip制备与处方的优化,制备的DLD/Hyp-Lip包封率高,粒径小,分布均匀,且具有良好的缓释作用,为DLD/Hyp-Lip的进一步体内研究奠定了基础。载金丝桃苷的DLD/Hyp-Lip具有良好的肝癌细胞线粒体靶向性,是一种潜在高效的肝癌细胞线粒体靶向给药系统。 相似文献
42.
《Drug discovery today》2022,27(8):2043-2050
43.
Jiao Yuan Wen-yu Yin Yang Wang Jun Chen Zhi-min Zhang Yong-xiang Tang Si-ya Pei Lin-xia Tan Xing-wang Hu Xue-gong Fan Ning Li 《Transfusion and apheresis science》2021,60(1):102930
Liver-targeted cargo delivery possesses great potential for the treatment of liver disease. It is urgent to find an efficient and biocompatible liver targeted delivery system. This study focused on the liver targeting properties of erythrocyte ghosts and its possible mechanism. Herein, we optimized conditions to fabricate human and mouse erythrocyte ghosts with sufficient room capable of incorporating various model substances. Erythrocyte ghosts are biocompatible cargo carriers because it is derived from autologous red blood cells (RBCs), and the cell size, zeta potential, and biconcave-disk shape of the ghosts were consistent with those of RBCs. An in vivo imaging system and positron emission tomography/computed tomography imaging showed that the ghosts were captured mainly in the liver by intravenous injection of fluorescence or 18F-fluorodeoxyglucose (FDG)-labelled ghosts into mice. In contrast, the main concentration of naked octreotide was trapped in the lungs while naked 18F-FDG was trapped in the heart. However, the concentration of cargo-loaded ghosts decreased significantly in the liver in macrophage-depleted mice. Accordingly, in vitro experiments showed that higher phosphatidylserine exposure was observed in the ghosts (38.9 %) compared to normal erythrocytes (0.69 %), and the phagocytic activity of the macrophage RAW 264.7. on the ghosts was significantly higher than that of normal erythrocytes (p < 0.001). Together they indicate that erythrocyte ghosts show liver targeting properties, and possibly owing to macrophage phagocytosis. This promising and effective therapeutic delivery system may provide therapeutic benefits for liver disease. 相似文献
44.
It has been well recognized that prolactin (PRL), a pleiotropic hormone, has many functions in the brain, such as maternal behavior, neurogenesis, and neuronal plasticity, among others. Recently, it has been reported to have a significant role in neuroprotection against excitotoxicity. Glutamate excitotoxicity is a common alteration in many neurological and neurodegenerative diseases, leading to neuronal death. In this sense, several efforts have been made to decrease the progression of these pathologies. Despite various reports of PRL’s neuroprotective effect against excitotoxicity, the signaling pathways that underlie this mechanism remain unclear. This review aims to describe the most recent and relevant studies on the molecular signaling pathways, particularly, PI3K/AKT, NF-κB, and JAK2/STAT5, which are currently under investigation and might be implicated in the molecular mechanisms that explain the PRL effects against excitotoxicity and neuroprotection. Remarkable neuroprotective effects of PRL might be useful in the treatment of some neurological diseases. 相似文献
45.
目的 构建基于超分子“气析”理论的中药制剂的靶向性评价方法,并对柴胡影响片仔癀的肝靶向性进行研究。方法 采用分子连接性指数分析主要归肝经的药材、片仔癀中的各成分“印迹模板”特征及肝靶向趋势;利用中药多成分“印迹模板”自主作用特征,结合靶区动力学和总量统计矩原理建立中药制剂的靶向性评价方法,并对片仔癀组、柴胡组、片仔癀+柴胡组、空白组4组作用的肝癌大鼠进行实验验证。结果 扣除主要归肝经药材分子连接性指数平均值后,片仔癀组与柴胡组的分子连接性指数相似度0.376 8,片仔癀+柴胡组与柴胡组的分子连接性指数相似度0.988 2,预测柴胡可增强片仔癀的肝靶向性。建立中药复方靶向性的评价体系,包括相对总量摄取率(RUET),相对总量浓度(RCT),相对“印迹”趋势(RITT)及相对“印迹”方差(RIVT);各组织中肝脏的RUET和RCT均为最大(RUET=1.88>1,RCT=2.30>1),其他组织这2个参数则均<1,说明片仔癀结合柴胡后能增加其在肝脏的分布,肝靶向性增强;除血浆外,其他组织的RITT及RIVT均在1.0附近波动,说明靶向修饰不改变片仔癀的“印迹”作用趋势,对成分种类也无明显影响。结论 在超分子“气析”理论指导下,可建立以分子连接性指数和总量统计矩参数表征中药制剂多成分“印迹”作用的靶向性评价参数体系,实现对中药制剂靶向性的评价,柴胡的加入可增加片仔癀的肝靶向性。 相似文献
46.
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48.
Ochratoxin A (OTA) is a mycotoxin that mainly causes nephrotoxicity. The single nephrotoxicity of OTA exposure on glomeruli or renal tubule had been well documented, however, the comparison toxicity between it is still unclear. Here, C57BL/6 mice and two types of nephrocyte were treated with concentration-gradient OTA to explore its differentiation nephrotoxicity. Results showed that OTA induced nephrotoxicity in vivo and in vitro, manifested as the deteriorative kidney function in mice and the cut-down cell viability in nephrocyte. Besides, results of murine kidney pathological section and IC50 of two types nephrocyte indicated that OTA-induced toxicity in renal tubule was higher than its in glomeruli. In addition, OTA exposure induced autophagy signaling differentiation expression. It revealed that autophagy was implicated in OTA-induced differential nephrotoxicity in glomeruli and renal tubule. Altogether, we proved that OTA induces a differentiation nephrotoxicity in glomeruli and renal tubule, and it is related to autophagy differential regulation. 相似文献
49.
《Drug discovery today》2022,27(8):2373-2385
Autophagy, an evolutionarily highly conserved cellular degradation process, plays the Janus role (either cytoprotective or death-promoting) in colorectal cancer, so the targeting of several key autophagic pathways with small-molecule compounds may be a new therapeutic strategy. In this review, we discuss autophagy-associated cell death pathways and key cytoprotective autophagy pathways in colorectal cancer. Moreover, we summarize a series of small-molecule compounds that have the potential to modulate autophagy-associated cell death or cytoprotective autophagy for therapeutic purposes. Taken together, these findings demonstrate the Janus role of autophagy in colorectal cancer, and shed new light on the exploitation of a growing number of small-molecule compounds to target autophagy in future cancer drug discovery. 相似文献
50.
《Saudi Pharmaceutical Journal》2022,30(12):1791-1801
Noscapine hydrochloride (benzyl-isoquinoline antitussive alkaloid) is an opium derivative and generally used as a cough suppressant. Numerous studies on noscapine hydrochloride have reported that it has potent anti-inflammatory activity. However, the mechanisms by which it exerts an anti-inflammatory function is not well understood. Protein denaturation is the primary step that leads to the organ destruction and permanent arthritic disability. The above-mentioned facts provided the ground to plan this study using different in-vitro and in-vivo approaches. RT-qPCR and ELISA assays were used to assess the inflammatory markers related to protein denaturation in complete adjuvant persuaded rheumatism in Sprague - Dawley rats. The results were collected as paw volume and body weight changes, arthritic scoring and serum antioxidant enzymes assays. These findings demonstrated that all doses of noscapine hydrochloride (10, 20 and 40 mg/kg) studied in this study, significantly (p < 0.001) decreased the protein denaturation by preventing the increase in levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nuclear factor-kB (NF-kB), cyclooxygenase-2 (COX-2) and prostaglandin E2. Noscapine hydrochloride significantly reduced the paw volume (p < 0.001), arthritic scoring and reversed the body mass as compared to arthritic control diseased rats. 相似文献