Department of Chemical Engineering and Materials Science, Sangmyung University, Seoul 110-743, Republic of Korea.
Department of Chemical Engineering and Materials Science, Sangmyung University, Seoul 110-743, Republic of Korea.
Int J Biol Macromol. 2021 Sep 30;187:399-408. doi: 10.1016/j.ijbiomac.2021.07.134. Epub 2021 Jul 24.
A novel chitosan-dipeptide hydrogel was fabricated through a combination of self-assembly of 9-fluorenylmethoxycarbonyl-modified diphenylalanine (Fmoc-FF) and its electrostatic interaction with glycol chitosan (GCS). Hydrogel strength and stability depended on its composition. The highest gel strength was observed at a Fmoc-FF mass fraction (ϕ) of 0.85, whereby the highest combined strength of the two interactions was achieved. As the ϕ increased above 0.6, gel stability decreased in buffered solution at pH 7.46. The incorporation of doxorubicin (DOX) as a cationic model drug significantly increased the stability of the complex hydrogels. DOX-loaded hydrogels exhibited slow DOX release, probably due to the drug's strong binding to Fmoc-FF via electrostatic attraction and the high gel stability. These hydrogels also exhibited excellent thixotropic features that facilitated the development of injectable self-healing drug delivery systems. Notably, DOX release was significantly accelerated as the pH of the medium decreased from 7.46 to 5.5 and 4.0, possibly due to hydrogel components' protonation. The DOX-loaded hydrogel exhibited notable cytotoxicity against A549 human lung cancer cells, which suggests the newly developed hydrogel to be a promising candidate vehicle for the localized and controlled drug delivery in cancer therapy.
一种新型壳聚糖二肽水凝胶是通过 9-芴甲氧羰基修饰的二苯丙氨酸（Fmoc-FF）的自组装及其与乙二醇壳聚糖（GCS）的静电相互作用相结合而制备的。水凝胶的强度和稳定性取决于其组成。在 Fmoc-FF 质量分数（ϕ）为 0.85 时观察到最高的凝胶强度，在此处实现了两种相互作用的最高组合强度。当 ϕ 高于 0.6 时，在 pH 值为 7.46 的缓冲溶液中凝胶稳定性降低。作为阳离子模型药物的阿霉素（DOX）的掺入显著增加了复杂水凝胶的稳定性。载 DOX 的水凝胶表现出缓慢的 DOX 释放，可能是由于药物通过静电吸引与 Fmoc-FF 强结合以及凝胶高稳定性所致。这些水凝胶还表现出出色的触变特性，有利于开发可注射的自修复药物输送系统。值得注意的是，当介质的 pH 值从 7.46 降低至 5.5 和 4.0 时，DOX 的释放明显加快，这可能是由于水凝胶成分的质子化。载 DOX 的水凝胶对 A549 人肺癌细胞表现出显著的细胞毒性，这表明新开发的水凝胶有望成为癌症治疗中局部和控制药物输送的候选载体。
