Department of Chemistry, Indian Institute of Technology Madras, Chennai 600 036, India.
Department of Chemistry, Indian Institute of Technology Madras, Chennai 600 036, India.
Mater Sci Eng C Mater Biol Appl. 2020 Jul;112:110857. doi: 10.1016/j.msec.2020.110857. Epub 2020 Mar 18.
A new group of non-ionic amphiphiles with short alkyl chains and functionalizable oxanorbornane-based head group for drug delivery application are presented. They can be prepared through a sequence that starts with cycloaddition of Boc-protected furfuryl amine with maleic anhydride and reduction of the resulting adduct with LiAlH to get a diol intermediate. Introduction of alkyl chains through these primary hydroxyl groups and subsequent head-group modification via cis-hydroxylation resulted in a number of new amphiphiles in good yields. They were characterized by various spectro-analytical techniques and then subjected to drug-delivery studies using ibuprofen as a model drug. Functionalization of the head group through the amine functionality was also done with an intention to improve lipid packing to get better drug-loading and release properties. Irrespective of the nature of groups attached through this amine unit, all amphiphiles with short alkyl chains were found to assemble into spherical aggregates when drop-casted from various organic solvents. The same assembly preference prevailed in their formulations containing lipid-cholesterol-drug in 1: 0.5:1 ratio as well, and these particles had diameters <300 nm. Apart from good drug-loading efficiencies, these amphiphiles exhibited controlled release properties and did not show any indication of toxicity when assayed against NIH3T3 cells. The formulation based on lipid having a phenylalanine unit on the head group (1.10c) turned out to be the best in this series which showed a loading efficiency of 57.6% with a controlled release of ~42% by end of 24 h. Because of efficient layering that is facilitated by hydrogen bonding involving well-directed hydroxyl groups on the head group, amphiphiles with alkyl chains as short as C5 are able to act as efficient drug delivery systems, which is one of the highlights of this work.
本文介绍了一组具有短烷基链和可功能化氧杂降冰片烯基头基的新型非离子两亲物，可用于药物输送应用。它们可以通过一系列步骤制备，首先是 Boc 保护的糠胺与马来酸酐的环加成，然后用 LiAlH 将得到的加合物还原得到二醇中间体。通过这些伯羟基引入烷基链，并通过顺式羟化对头基进行修饰，得到了一系列新的两亲物，产率良好。它们通过各种光谱分析技术进行了表征，然后用布洛芬作为模型药物进行了药物输送研究。通过伯胺官能团对头基进行功能化，目的是改善脂质堆积，获得更好的载药和释放性能。无论通过这个胺单元连接的基团的性质如何，所有具有短烷基链的两亲物在从各种有机溶剂中滴铸时都被发现组装成球形聚集体。在含有脂质-胆固醇-药物的比例为 1:0.5:1 的配方中，同样存在这种组装偏好，这些颗粒的直径<300nm。除了良好的载药效率外，这些两亲物还表现出控制释放性能，在对 NIH3T3 细胞进行测试时没有显示出任何毒性迹象。基于头部基团上带有苯丙氨酸单元的脂质的配方（1.10c）在该系列中表现最佳，其载药效率为 57.6%，在 24 小时结束时控制释放约 42%。由于头部基团上定向良好的羟基参与的氢键促进了有效的分层，短至 C5 的烷基链两亲物能够作为有效的药物输送系统，这是这项工作的亮点之一。
