Smith Cartney E, Kong Hyunjoon
Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign , 600 South Mathews Avenue, Urbana, Illinois, 61801 United States.
Langmuir. 2014 Apr 8;30(13):3697-704. doi: 10.1021/la500412r. Epub 2014 Mar 25.
Liposomes are commonly used to deliver drugs and contrast agents to their target site in a controlled manner. One of the greatest obstacles in the performance of such delivery vehicles is their stability in the presence of serum. Here, we demonstrate a method to stabilize a class of liposomes that load gadolinium, a magnetic resonance (MR) contrast agent, as a model cargo on their surfaces. We hypothesized that the sequential adsorption of a gadolinium-binding chitosan fastener on the liposome surface followed by covalent cross-linking of the lipid bilayer would provide enhanced stability and improved MR signal in the presence of human serum. To investigate this hypothesis, liposomes composed of diyne-containing lipids were assembled and functionalized via chitosan conjugated with a hydrophobic anchor and diethylenetriaminepentaacetic acid (DTPA). This postadsorption cross-linking strategy served to stabilize the thermodynamically favorable association between liposome and polymeric fastener. Furthermore, the chitosan-coated, cross-linked liposomes proved more effective as delivery vehicles of gadolinium than uncross-linked liposomes due to the reduced liposome degradation and chitosan desorption. Overall, this study demonstrates a useful method to stabilize a broad class of particles used for systemic delivery of various molecular payloads.
脂质体通常用于以可控方式将药物和造影剂递送至其靶位点。此类递送载体性能方面最大的障碍之一是它们在血清存在下的稳定性。在此，我们展示了一种稳定一类脂质体的方法，这类脂质体在其表面负载钆（一种磁共振（MR）造影剂）作为模型货物。我们假设钆结合壳聚糖紧固件在脂质体表面的顺序吸附，随后脂质双层的共价交联，将在人血清存在下提供增强的稳定性并改善MR信号。为了研究这一假设，由含二炔脂质组成的脂质体通过与疏水锚和二乙三胺五乙酸（DTPA）共轭的壳聚糖进行组装和功能化。这种吸附后交联策略有助于稳定脂质体与聚合物紧固件之间热力学上有利的结合。此外，由于脂质体降解和壳聚糖解吸减少，壳聚糖包被的交联脂质体作为钆的递送载体比未交联的脂质体更有效。总体而言，本研究展示了一种稳定用于各种分子载荷全身递送的一大类颗粒的有用方法。
