Chandra Binita, Subramaniam Rajesh, Mallik Sanku, Srivastava D K
Department of Pharmaceutical Sciences, North Dakota State University, Fargo, 58105, USA.
Org Biomol Chem. 2006 May 7;4(9):1730-40. doi: 10.1039/b518359f. Epub 2006 Mar 29.
In pursuit of designing photocleavable liposomes as drug delivery vehicles, we synthesized several amphiphilic lipids by connecting stearyl amine (as the non-polar tail) and charged amino acids (as polar heads) via the o-nitrobenzyl derivatives. The lipids containing Glu, Asp, and Lys amino acids were subjected to photocleavage reaction by UV light, and the overall spectral changes of the chromophoric o-nitrobenzyl conjugates were determined as a function of time. The experimental data revealed that the feasibility of the cleavage reaction, nature and magnitude of the spectral changes during the course of the cleavage reaction, and their overall kinetic profiles were dictated by the type of amino acid constituting the polar head groups. The cleavage reactions of the Asp and Glu containing lipids were found to be more facile than that of the lysine-containing lipid. Using these lipids, we formulated photocleavable liposomes, and investigated the photo-triggered release of an encapsulated (within the liposomal lumen) dye as a function of time. The kinetic data revealed that the release of the liposomal content conformed to a two-step mechanism, of which the first (fast) step involved the photocleavage of lipids followed by the slow release of the liposomal content during the second step. The overall mechanistic features intrinsic to the photocleavage of Asp, Glu and Lys containing o-nitrobenzyl conjugated lipids, and their potential applications in formulating liposomes (whose contents can be "unloaded" by the UV light) as drug delivery vehicles are discussed.
为了设计可光裂解脂质体作为药物递送载体，我们通过邻硝基苄基衍生物连接硬脂胺（作为非极性尾部）和带电荷的氨基酸（作为极性头部）合成了几种两亲性脂质。含有谷氨酸、天冬氨酸和赖氨酸的脂质通过紫外光进行光裂解反应，并测定发色团邻硝基苄基共轭物的整体光谱变化随时间的函数关系。实验数据表明，裂解反应的可行性、裂解反应过程中光谱变化的性质和幅度及其整体动力学曲线取决于构成极性头部基团的氨基酸类型。发现含天冬氨酸和谷氨酸的脂质的裂解反应比含赖氨酸的脂质更容易。使用这些脂质，我们制备了可光裂解脂质体，并研究了包封在脂质体腔内的染料随时间的光触发释放。动力学数据表明，脂质体内容物的释放符合两步机制，其中第一步（快速）涉及脂质的光裂解，随后第二步是脂质体内容物的缓慢释放。本文讨论了含天冬氨酸、谷氨酸和赖氨酸的邻硝基苄基共轭脂质光裂解的内在整体机制特征，以及它们在制备脂质体（其内容物可通过紫外光“卸载”）作为药物递送载体方面的潜在应用。
