共查询到20条相似文献,搜索用时 46 毫秒
1.
2.
肿瘤作为全球危害人类健康的重大疾病之一,亟需寻找更加安全高效的治疗方案。核糖核酸(ribonucleic acid, RNA)药物的基因疗法可以调节肿瘤相关基因的表达,已在临床前和临床试验中展示出良好的抗肿瘤治疗潜力。基于肿瘤组织在pH、特异性酶浓度或氧化还原梯度变化等微环境信号特征与正常组织存在差异性,各类微环境响应型纳米载体正在被研究开发用于递送RNA药物,实现对肿瘤组织与细胞的靶向递送,提高RNA药物的抗肿瘤疗效并且降低不良反应。本文综述了肿瘤微环境的病生理特征以及各类肿瘤微环境响应型载体策略,旨在为设计安全高效的RNA药物肿瘤靶向递送系统提供参考。 相似文献
3.
作为抗肿瘤治疗的主要手段,化疗最大的缺陷在于化疗药物缺乏肿瘤靶向性,易对正常组织产生高毒性,并导致治疗效果不理想。为了解决这一问题,越来越多的聚合物纳米载体被用于递送抗肿瘤药物,包括对温度刺激能作出响应的温敏聚合物自组装纳米载体。笔者综述了近年来温敏聚合物自组装载体及其纳米粒子的研究进展,并介绍了其在抗肿瘤药物递送中的应用。 相似文献
4.
随着生物纳米技术在药物递送领域的深入研究和广泛应用,研究人员设计和构建多种功能各异的纳米药物递送系统用于抗肿瘤药物的高效递送。其中,将前药策略与纳米递药技术进行有机整合的前药纳米组装体已经逐渐成为纳米药物递送系统中一个非常重要的领域。前药设计的关键在于药物分子结构的合理修饰和前药在靶部位的选择性高效激活。近年来,研究发现肿瘤微环境智能响应型前药纳米组装体能够在靶部位选择性快速释药,其已成为癌症诊疗相关研究的重要平台。首先,对肿瘤氧化还原微环境和常用的氧化还原敏感化学桥连进行介绍;其次,分别介绍肿瘤氧化还原微环境智能响应型聚合物大分子前药纳米组装体和小分子前药纳米组装体;最后,对前药纳米组装体优缺点和整个纳米药物递送系统的临床转化前景进行总结和分析。通过对以上内容进行综述,以期为肿瘤微环境智能响应型前药纳米系统的设计与构建提供参考。 相似文献
5.
基因治疗在临床转化和应用方面取得了许多瞩目的进展。然而,基因治疗面临的主要挑战仍是如何安全有效地递送核酸药物,尤其是实现对靶细胞的按需递送。基于疾病部位异常的氧化还原环境,研究者设计了众多氧化还原响应型核酸药物递送系统。该类递送系统中的氧化还原敏感基团在被氧化或被还原后触发结构断裂或性质转变,从而实现核酸药物在疾病部位的特异性释放,提高疗效。综述了各类氧化还原响应型核酸递送系统的设计思路和原理,并探讨其在肿瘤、炎症等治疗中的应用和发展前景,以期为核酸药物递送系统的发展和临床转化提供参考。 相似文献
6.
肿瘤微环境的复杂性为肿瘤靶向递药带来挑战的同时也赋予其一定的机遇。一方面,通过利用肿瘤微环境的特征信号为刺激源,构建各种各样的响应性递药系统,可实现药物在肿瘤部位的靶向递送;另一方面,肿瘤部位异质的新生血管和异生的胶原等所引起的较高的固体瘤压力及肿瘤间质压等成为药物递送的巨大障碍,极大地降低了递药系统的递送效率。许多研究致力于通过调节肿瘤微环境,使其更利于药物在肿瘤部位的递送。本文综述了基于肿瘤微环境响应性纳米递药系统的设计及调节肿瘤微环境以提高肿瘤靶向递送效率的最新进展,并对其中存在的问题及未来的发展进行讨论。 相似文献
7.
8.
9.
癌症是威胁人类生存的恶性疾病之一。近年来,利用纳米技术将药物靶向递送到肿瘤部位,可以增加疗效并降低毒性,为癌症治疗带来了新希望。壳聚糖是自然界唯一存在的碱性多糖,具有良好的生物相容性和生物可降解性。此外,其反应位点多,可制成不同性质的衍生物,广泛用于药物递送系统和组织工程支架,在生物医药领域具有重要的应用价值。本综述对近年来壳聚糖纳米粒在抗癌药物递送方面的研究进展进行介绍,重点介绍了壳聚糖纳米粒的制备、被动靶向、主动靶向和刺激-响应药物递送系统方面的研究进展。 相似文献
10.
11.
M. ASHTON 《Xenobiotica; the fate of foreign compounds in biological systems》2013,43(2):195-204
1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species. 相似文献
12.
Ashton M Johansson L Thornqvist AS Svensson US 《Xenobiotica; the fate of foreign compounds in biological systems》1999,29(2):195-204
1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species. 相似文献
13.
J P KNOWLES 《British medical journal》1961,2(5264):1396-1399
14.
Boobis AR 《Environmental toxicology and pharmacology》1996,2(2-3):161-163
In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process. 相似文献
15.
Markus Müller Bettina v.Osten Rainer Schmid Evelyne Piegler Ingeborg Gerngroß 《Naunyn-Schmiedeberg's archives of pharmacology》1995,352(4):438-441
Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (cmax, tmax, AUC) were calculated for plasma and tissue time courses. The mean AUCtissue /AUCplasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA
Fluorescence polarisation immuno assay
- AUC
Area under the curve
- tmax
Time to peak concentration
- cmax
Peak concentration 相似文献
16.
本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。 相似文献
17.
AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix. 相似文献
18.
LEATHER HM 《British medical journal》1960,1(5190):1930-1938
19.
Trichinellosis in immigrants in Switzerland 总被引:1,自引:0,他引:1
Lozano Becera JC Gurtner De la Fuente V Pozio E Bernasconi E 《Journal of travel medicine》2012,19(3):195-197
We describe a case of trichinellosis diagnosed at the Division of Infectious Diseases, Hospital of Lugano, in January 2009. This case was associated with a cluster of cases and was traced to the consumption of contaminated meat after a wild boar hunt in Bosnia. 相似文献
20.