PEG脂质插入药物脂质体后的定量在单个脂质体水平,Advanced Materials Interfaces

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PEG脂质插入药物脂质体后的定量在单个脂质体水平
Advanced Materials Interfaces ( IF 4.3 ) Pub Date : 2019-04-03 , DOI: 10.1002/admi.201801807
Rasmus Eliasen ₁ , Thomas L. Andresen ₁ , Jannik B. Larsen ₁

Affiliation

脂质体给药系统的设计避免了人体的自然清除机制，通常是通过掺入脂质锚定的聚乙二醇（PEG）聚合物来实现的。在制备此类脂质体时，本质上假设所有可用的PEG-脂质均等地掺入到制剂的每个脂质体中，但是这一假设仍然没有挑战。因此，对PEG脂质掺入条件如何影响单个脂质体上PEG密度的定量理解可以为如何优化脂质体循环动力学和治疗功效的重要参数提供新颖的见解。在这里，采用了一种基于荧光的灵敏的单脂质体测定方法，该方法首次实现了对单个脂质体上PEG脂质密度的定量分析。该测定用于证明孵育时间和温度，脂质体膜脂质饱和状态和PEG锚定部分均会影响有效PEG表面密度。此外，该测定法研究集合中单个脂质体的独特能力，可以量化单个脂质体之间PEG表面密度的显着变化。因此，该测定法提供了关于如何改善整体PEG表面密度和减少脂质体到脂质体变异的关键见解，从而有助于设计和开发更均匀，可控制和有效的PEG脂质脂质体药物递送系统。该测定法研究集合中单个脂质体的独特能力，可以量化单个脂质体之间PEG表面密度的显着变化。因此，该测定法提供了关于如何改善整体PEG表面密度并减少脂质体到脂质体变异的关键见解，从而有助于设计和开发更均匀，可控制且有效的PEG脂质脂质体药物递送系统。该测定法研究集合中单个脂质体的独特能力，可以量化单个脂质体之间PEG表面密度的显着变化。因此，该测定法提供了关于如何改善整体PEG表面密度并减少脂质体到脂质体变异的关键见解，从而有助于设计和开发更均匀，可控制且有效的PEG脂质脂质体药物递送系统。

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PEG‐Lipid Post Insertion into Drug Delivery Liposomes Quantified at the Single Liposome Level

Liposomal drug delivery systems are designed to avoid the body's natural clearance machinery and are typically achieved by incorporation lipid‐anchored poly(ethylene glycol) (PEG) polymers. When preparing such liposomes it is intrinsically assumed that all available PEG‐lipid is incorporated evenly into every liposome of a preparation, however this assumption remains unchallenged. Thus, a quantitative understanding of how PEG‐lipid incorporation conditions affect the PEG density on individual liposomes can provide novel insights on how to optimize an important parameter of liposomal circulation kinetics and therapeutic efficacy. Here a sensitive fluorescence‐based single liposome assay is employed that allows, for the first time, the quantification of the PEG‐lipid density on individual liposomes. The assay is used to demonstrate that incubation time and temperature, liposome membrane lipid saturation state and PEG anchoring moiety all affect the effective PEG surface density. Furthermore, the unique ability of the assay to investigate single liposomes within the ensemble, allows to quantify significant variations in PEG surface density between individual liposomes. Thus, the assay provides crucial insights on how to improve both the overall PEG surface density and reduce the liposome‐to‐liposome variation, facilitating the design and development of more uniform, controllable, and efficacious PEG‐lipid containing liposomal drug delivery systems.

更新日期：2019-04-03

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