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纳米复合物治疗囊型和泡型包虫病的疗效:挑战与展望。

Therapeutic efficacy of nanocompounds in the treatment of cystic and alveolar echinococcoses: challenges and future prospects.

机构信息

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Department of Parasitology and Mycology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Parasitol Res. 2019 Sep;118(9):2455-2466. doi: 10.1007/s00436-019-06416-5. Epub 2019 Aug 11.

Abstract

Echinococcus granulosus sensu lato and E. multilocularis are the causative agents of life-threatening cystic and alveolar echinococcoses (CE and AE), respectively, which lead to serious public health concerns across the globe. Benzimidazoles (BMZs) are the drugs of choice for the treatment of human CE and AE. Presently, the chemotherapeutic failures of BMZs against CE and AE are caused by their low aqueous solubility, poor absorption, and consequently their erratic bioavailability. Among the BMZ compounds used for CE/AE treatment, albendazole (ABZ) and mebendazole (MBZ) are the only drugs licensed for human use. Nevertheless, the administration of these BMZs for a long period of time leads to undesirable adverse effects. Therefore, there is an urgent need for designing new formulations of BMZs with increased bioavailability. To bridge these therapeutic gaps, nanoparticle enantiomers of ABZ and drug delivery systems based on nanostructured entities currently provide an interesting new formulation of already existing drugs to improve the pharmacokinetic effects of BMZs. This study provides an overview of the tested nanocompounds against E. granulosus and E. multilocularis, including their effective dose, type of nanoparticles (NPs), assay setting, and therapeutic outcomes. This review suggests that BMZ derivatives loaded in NPs can significantly improve the scolicidal and cysticidal activities compared with single BMZ. Moreover, BMZ-loaded polymeric NPs show a tendency to increase mortality rate against protoscoleces and microcysts compared with metallic formulations, nanoemulsions, lipid nanocapsules, solid lipid NPs, liposomes, and nanocrystals. In the future, the use of the newly structured entities, attained by bridging ligands to the modified surface of NPs, as well as the electromagnetically produced nanodrugs could be helpful for developing fine-tuned formulations as an alternative to the already existing drugs against these neglected parasitic infections.

摘要

细粒棘球蚴和多房棘球绦虫分别是致命性的囊型和泡型棘球蚴病(CE 和 AE)的病原体,这在全球范围内引起了严重的公共卫生关注。苯并咪唑类药物(BMZs)是治疗人类 CE 和 AE 的首选药物。目前,BMZ 治疗 CE 和 AE 的化疗失败是由于其低水溶性、吸收不良,进而导致其生物利用度不稳定。在用于 CE/AE 治疗的 BMZ 化合物中,阿苯达唑(ABZ)和甲苯达唑(MBZ)是唯一获准用于人类的药物。然而,长期使用这些 BMZ 会导致不良的不良反应。因此,迫切需要设计具有更高生物利用度的 BMZ 新制剂。为了弥补这些治疗空白,ABZ 的纳米粒子对映体和基于纳米结构实体的药物传递系统目前为改善 BMZ 的药代动力学效果提供了一种有趣的现有药物新制剂。本研究综述了针对细粒棘球蚴和多房棘球绦虫的测试纳米复合物,包括其有效剂量、纳米粒子(NPs)类型、检测设置和治疗结果。本综述表明,与单一 BMZ 相比,负载在 NPs 中的 BMZ 衍生物可以显著提高杀棘球蚴和杀囊虫活性。此外,与金属制剂、纳米乳液、脂质纳米胶囊、固体脂质 NPs、脂质体和纳米晶体相比,负载 BMZ 的聚合物 NPs 显示出增加原头蚴和微囊死亡率的趋势。在未来,通过将桥连配体连接到 NPs 的改性表面来获得的新结构实体以及通过电磁产生的纳米药物的使用可能有助于开发精细调整的制剂,作为这些被忽视的寄生虫感染的现有药物的替代物。

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