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隐形脂质在基于纳米医学的药物载体中的作用。

Role of stealth lipids in nanomedicine-based drug carriers.

机构信息

Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Pilani Campus, Rajasthan, 333031, India.

Department of Biotechnology, Birla Institute of Technology and Science, Pilani (BITS-PILANI), Dubai Campus, Dubai, United Arab Emirates.

出版信息

Chem Phys Lipids. 2021 Mar;235:105036. doi: 10.1016/j.chemphyslip.2020.105036. Epub 2021 Jan 5.

Abstract

The domain of nanomedicine owns a wide-ranging variety of lipid-based drug carriers, and novel nanostructured drug carriersthat are further added to this range every year. The primary goal behind the exploration of any new lipid-based nanoformulation is the improvement of the therapeutic index of the concerned drug molecule along with minimization in the associated side-effects. However, for maintaining a sustained delivery of these intravenously injected lipoidal nanomedicines to the targeted tissues and organ systems in the body, longer circulation in the bloodstream, as well as their stability, are important. After administration, upon recognition as foreign entities in the body, these systems are rapidly cleared by the cells associated with the mononuclear phagocyte system. In order to provide these lipid-based systems with long circulation characteristics, techniques such as coating of the lipoidal surface with an inert polymeric material like polyethylene glycol (PEG) assists in imparting 'stealth properties' to these nanoformulations for avoiding recognition by the macrophages of the immune system. In this review, detailed importance is given to the hydrophilic PEG polymer and the role played by PEG-linked lipid polymers in the field of nanomedicine-based drug carriers. The typical structure and classification of stealth lipids, clinical utility, assemblage techniques, physicochemical characterization, and factors governing the in-vivo performance of the PEG-linked lipids containing formulations will be discussed. Eventually, the novel concept of accelerated blood clearance (ABC) phenomenon associated with the use of PEGylated therapeutics will be deliberated.

摘要

纳米医学领域拥有广泛的基于脂质的药物载体,并且每年都会有新的纳米结构药物载体加入到这个领域。探索任何新的基于脂质的纳米制剂的主要目标是提高相关药物分子的治疗指数,同时最小化相关副作用。然而,为了维持这些静脉注射脂质纳米药物在体内靶向组织和器官系统的持续递送,更长的血液循环时间以及它们的稳定性是很重要的。给药后,这些系统在体内被识别为外来实体后,会被与单核吞噬细胞系统相关的细胞迅速清除。为了给这些基于脂质的系统提供长循环特性,用惰性聚合物材料(如聚乙二醇(PEG))对脂质表面进行涂层等技术有助于为这些纳米制剂赋予“隐身特性”,以避免被免疫系统的巨噬细胞识别。在这篇综述中,详细介绍了亲水性 PEG 聚合物以及 PEG 连接的脂质聚合物在基于纳米医学的药物载体领域中的作用。将讨论隐身脂质的典型结构和分类、临床应用、组装技术、物理化学特性以及影响含 PEG 脂质制剂体内性能的因素。最终,将讨论与使用 PEG 化治疗剂相关的新型血液清除加速(ABC)现象的概念。

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