Novel analytical methods to assess the chemical and physical properties of liposomes
Novel analytical methods to assess the chemical and physical properties of liposomes
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DOI：
10.1016/j.jchromb.2018.05.028
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发表时间：
2018-08-01
影响因子：
3
通讯作者：
Linder, Sean W.
中科院分区：
文献类型：
--
作者：
Kothalawala, Nuwan;Mudalige, Thilak K.;Linder, Sean W.
脂质体用于商业药物制剂（PFs）和膳食补充剂（DSs）作为载体，以保护活性成分不被降解，并延长注射药物的半衰期。尽管脂质体产品的商业化迅速增加，但评价脂质体产品物理和化学性质的表征方法尚未建立。在这里，我们发展快速的方法来评估化学和选定的物理性质的脂质体制剂。脂质体的化学性质是由它们的脂质组成决定的。脂质组成评估首先使用HPLC-ELSD筛选样品中的脂质，然后使用HPLC-MSMS进行高质量精度（< 5 ppm）分析，碎片模式和脂质结构数据库搜索。利用可调电阻脉冲传感技术（TRPS）研究了其粒度和粒度分布等物理性质。开发的方法用于分析市售的PFs和DSs。结果表明，PFs含有不同数量的脂质，但DSs更复杂，含有大量属于不同亚类的脂质。市售脂质体具有基于TRPS进行的尺寸测量的宽尺寸分布的颗粒。高质量精度以及使用多片段离子识别脂质有助于准确识别脂质并将其与其他亲脂分子区分开来。所开发的分析方法已成功地用于测量商业脂质体的理化性质。
Liposomes are used in commercial pharmaceutical formulations (PFs) and dietary supplements (DSs) as a carrier vehicle to protect the active ingredient from degradation and to increase the half-life of the injectable. Even as the commercialization of liposomal products has rapidly increased, characterization methodologies to evaluate physical and chemical properties of the liposomal products have not been well-established. Herein we develop rapid methodologies to evaluate chemical and selected physical properties of liposomal formulations. Chemical properties of liposomes are determined by their lipid composition. The lipid composition is evaluated by first screening of the lipids present in the sample using HPLC-ELSD followed by HPLC-MSMS analysis with high mass accuracy (< 5 ppm), fragmentation pattern and lipid structure databases searching. Physical properties such as particle size and size distribution were investigated using Tunable Resistive Pulse Sensing (TRPS). The developed methods were used to analyze commercially available PFs and DSs. As results, PFs contain distinct number of lipids as indicated by the manufacture, but DSs were more complicated containing a large number of lipids belonging to different sub-classes. Commercially available liposomes have particles with wide size distribution based on size measurements performed by TRPS. The high mass accuracy as well as identification lipids using multiple fragment ions aided to accurately identify the lipids and differentiate them from other lipophilic molecules. The developed analytical methodologies were successfully adapted to measure the physiochemical properties of commercial liposomes.