Lim Shaun W Z, Wong Yee Shan, Czarny Bertrand, Venkatraman Subbu
School of Materials Science & Engineering, Nanyang Technological University, Singapore 639798, Singapore.
School of Materials Science & Engineering, Nanyang Technological University, Singapore 639798, Singapore.
J Colloid Interface Sci. 2020 Oct 15;578:47-57. doi: 10.1016/j.jcis.2020.05.114. Epub 2020 Jun 2.
Microfluidics has been used to process self-assembling liposomal systems that are commonly considered for drug delivery applications. However, it has been found that the parameters of the process are not universally suited for all lipid types. We hypothesize here that size aggregation and instability of microfluidic liposomes are a direct consequence of the presence of interdigitation in these liposomes. Interdigitation refers to the phenomenon where two opposing leaflets of a bilayer interpenetrate into one another and form a single layer. When this happens, aggregation results as the single layer is not thermodynamically stable. Such interdigitation can be induced by pressure, chemicals or by the type of lipid structure. In this study, we systematically investigate the role of lipid composition on membrane interdigitation in order to understand the dependency of lipid interdigitation on liposome formation by microfluidics. By doing so, we use nano DSC and SAXS to probe the extent of lipid interdigitation by measuring the changes in thermodynamics and membrane thickness of the lipid bilayers. Our results show that microfluidic-fabricated liposomes undergo chemical interdigitation in the presence of ethanol, in particular saturated 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). Strategies to prevent interdigitation is to either remove ethanol above the lipid's main transition temperature (T), preventing the formation of interdigitated structures and subsequent aggregated states or by the incorporation of the inhibiting additives, such as cholesterol.
微流控技术已被用于处理常用于药物递送应用的自组装脂质体系统。然而，人们发现该过程的参数并非普遍适用于所有脂质类型。我们在此假设，微流控脂质体的尺寸聚集和不稳定性是这些脂质体中存在交叉指化现象的直接结果。交叉指化是指双层膜的两个相对小叶相互渗透并形成单层的现象。当这种情况发生时，由于单层在热力学上不稳定，就会导致聚集。这种交叉指化可以由压力、化学物质或脂质结构类型诱导。在本研究中，我们系统地研究了脂质组成对膜交叉指化的作用，以了解脂质交叉指化对微流控脂质体形成的依赖性。为此，我们使用纳米差示扫描量热法（nano DSC）和小角X射线散射法（SAXS），通过测量脂质双层热力学和膜厚度的变化来探测脂质交叉指化的程度。我们的结果表明，在乙醇存在下，特别是饱和的1,2 - 二棕榈酰 - sn - 甘油 - 3 - 磷酸胆碱（DPPC），微流控制备的脂质体会发生化学交叉指化。防止交叉指化的策略是在脂质的主要转变温度（T）以上去除乙醇，防止形成交叉指化结构和随后的聚集状态，或者通过加入抑制添加剂，如胆固醇。
