Kaplan Seref, Colak Mehmet, Hosgoren Halil, Pirinccioglu Necmettin
Department of Chemistry, Faculty of Science, Dicle University, 21280 Diyarbakir, Turkey.
ACS Omega. 2019 Jul 18;4(7):12342-12356. doi: 10.1021/acsomega.9b01086. eCollection 2019 Jul 31.
This work reports on the synthesis of three new l-lysine-based organogelators bis(N-alkanoyl-N-l-lysyl ethylester)oxalylamides, where alkanoyls are lauroyl, myristoyl, and palmitoyl. The gels of these gelators were prepared with high yields in eco-friendly solvents commonly used in cosmetics such as ethyl and isopropyl esters of lauric and myristic acids, liquid paraffin, 1-decanol, and 1,2-propanediol. Fourier transform infrared measurements revealed the involvement of intermolecular hydrogen bonds in the gelation. Scanning electron microscopy images of xerogels indicated different morphologic patterns with regard to the alkanoyl chain length and the solvent employed in their preparation. The gel formation was supported by rheological measurements. Three gels prepared in liquid paraffin were loaded with naproxen (Npx) with a quite high loading capacity (up to 166.6% as percentage of gelator) without gel disruption. The release of Npx from the gel matrix into the buffered solution at physiologic pH was evaluated using UV-vis spectroscopy. The results revealed that the release rate of Npx from the organogels significantly retarded with increasing organogelator concentration, whereas it enhanced with increasing Npx concentration. The rate was also found to be pH-dependent; the lower the pH, the lower the rate. Furthermore, molecular dynamic calculations performed on the octamer of myristoyl-bearing gelator ( ) in 1,2-propanediol provided useful information regarding the structural properties of the gels, which may be of interest to interpret the structure of the gel matrix. Altogether, this work provided valuable outcomes, which may be relevant to the pharmaceutical industry. It may be suggested that l-lysine-based gels have potentials in the delivery of nonsteroidal anti-inflammatory drug molecules. Besides, the release of the drug can be fine-tuned by the correct choice of gelator-solvent combination.
本研究报道了三种基于L-赖氨酸的新型有机凝胶剂双（N-烷酰基-N-L-赖氨酰乙酯）草酰胺的合成，其中烷酰基分别为月桂酰、肉豆蔻酰和棕榈酰。这些凝胶剂在化妆品常用的环保溶剂中能高产率地制备凝胶，如月桂酸和肉豆蔻酸的乙酯和异丙酯、液体石蜡、1-癸醇和1,2-丙二醇。傅里叶变换红外测量表明分子间氢键参与了凝胶化过程。干凝胶的扫描电子显微镜图像显示，根据烷酰基链长度和制备过程中使用的溶剂不同，呈现出不同的形态模式。流变学测量支持了凝胶的形成。在液体石蜡中制备的三种凝胶负载了萘普生（Npx），负载量相当高（高达凝胶剂百分比的166.6%）且未破坏凝胶。使用紫外-可见光谱法评估了Npx从凝胶基质在生理pH值下释放到缓冲溶液中的情况。结果表明，随着有机凝胶剂浓度的增加，Npx从有机凝胶中的释放速率显著减慢，而随着Npx浓度的增加而加快。还发现释放速率与pH有关；pH越低，速率越低。此外，对含肉豆蔻酰的凝胶剂八聚体在1,2-丙二醇中的分子动力学计算提供了有关凝胶结构性质的有用信息，这可能有助于解释凝胶基质的结构。总之，这项工作提供了有价值的成果，可能与制药行业相关。可以认为基于L-赖氨酸的凝胶在非甾体抗炎药物分子的递送方面具有潜力。此外，通过正确选择凝胶剂-溶剂组合可以微调药物的释放。
