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脂质体药物递送系统技术的创新及其在各种疾病治疗中的应用。

Innovations in Liposomal DDS Technology and Its Application for the Treatment of Various Diseases.

作者信息

Oku Naoto

机构信息

Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka.

出版信息

Biol Pharm Bull. 2017;40(2):119-127. doi: 10.1248/bpb.b16-00857.

Abstract

Liposomes have been widely used as drug carriers in the field of drug delivery systems (DDS), and they are thought to be ideal nano-capsules for targeting DDS after being injected into the bloodstream. In general, DDS drugs meet the needs of aged and super-aged societies, since the administration route of drugs can be changed, the medication frequency reduced, the adverse effects of drugs suppressed, and so on. In fact, a number of liposomal drugs have been launched and used worldwide including liposomal anticancer drugs, and these drugs have appeared on the market owing to various innovations in liposomal DDS technologies. The accumulation of long-circulating liposomes in cancer tissue is driven by the enhanced permeability and retention (EPR) effect. In this review, liposome-based targeting DDS for cancer therapy is briefly discussed. Since cancer angiogenic vessels are the ideal target of drug carriers after their injection and are critical for cancer growth, damaging of these neovessels has been an approach for eradicating cancer cells. Also, the usage of liposomal DDS for the treatment of ischemic stroke is possible, since we observed that PEGylated liposomes accumulate in the site of cerebral ischemia in transient middle cerebral artery occlusion (t-MCAO) model rats. Interestingly, liposomes carrying neuroprotectants partly suppress ischemia/reperfusion injury of these model rats, suggesting that the EPR effect also works in ischemic diseases by causing an increase in the permeability of the blood vessel endothelium. The potential of liposomal DDS against life-threatening diseases might thus be attractive for supporting long-lived societies.

摘要

脂质体作为药物载体在药物递送系统(DDS)领域已得到广泛应用,并且被认为是注入血液后用于靶向DDS的理想纳米胶囊。一般来说,DDS药物满足了老龄化和超老龄化社会的需求,因为药物的给药途径可以改变,用药频率降低,药物的不良反应得到抑制等等。事实上,包括脂质体抗癌药物在内的多种脂质体药物已在全球范围内推出并使用,这些药物由于脂质体DDS技术的各种创新而上市。长循环脂质体在癌组织中的蓄积是由增强的渗透和滞留(EPR)效应驱动的。在本综述中,简要讨论了基于脂质体的癌症治疗靶向DDS。由于癌症血管生成性血管是药物载体注射后的理想靶点,并且对癌症生长至关重要,破坏这些新生血管一直是根除癌细胞的一种方法。此外,脂质体DDS用于治疗缺血性中风也是可能的,因为我们观察到聚乙二醇化脂质体在短暂性大脑中动脉闭塞(t-MCAO)模型大鼠的脑缺血部位蓄积。有趣的是,携带神经保护剂的脂质体部分抑制了这些模型大鼠的缺血/再灌注损伤,这表明EPR效应也通过引起血管内皮通透性增加而在缺血性疾病中起作用。因此,脂质体DDS对抗危及生命疾病的潜力可能对支持长寿社会具有吸引力。

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