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疏水改性明胶水凝胶作为带电荷亲水药物和疏水药物的载体。

Hydrophobically-modified gelatin hydrogel as a carrier for charged hydrophilic drugs and hydrophobic drugs.

机构信息

Department of Chemical Engineering, Graduate School of Science and Engineering, Kagoshima University, 1-21-40 Korimoto, Kagoshima 890-0065, Japan.

Department of Chemical Engineering, Graduate School of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0385, Japan.

出版信息

Int J Biol Macromol. 2020 Apr 15;149:140-147. doi: 10.1016/j.ijbiomac.2020.01.227. Epub 2020 Jan 23.

Abstract

Gelatin molecules have been chemically crosslinked using potentially cytotoxic reagents to prepare stable hydrogels. Hydrophobic interaction is a means of forming physical crosslinks that is a good candidate for enhancing the stability of gelatin hydrogels without using cytotoxic chemicals. In this study, we proposed a new method to fabricate hydrogels from hydrophobically-modified gelatin (HMG) with high content of hydrophobic segments. HMG was first dissolved in dimethyl sulfoxide and poured into a vial with the desired shape. After the solution was freeze-dried, the solid construct was hydrated. The HMG hydrogel containing basic fibroblast growth factor promoted angiogenesis in vivo, indicating that the positively charged hydrophilic growth factor formed an electrostatic complex with negatively charged HMG hydrogel and was gradually released in vivo with the degradation of the hydrogel. In addition, we showed that the hydrophobic segments of HMG enhanced the adsorption of fluorescein sodium, a model for hydrophobic therapeutic agents, to the hydrogel through hydrophobic interaction. Furthermore, in vitro experiments indicated that the hydrophobic agents would be released from the hydrogel in a controlled manner in vivo. These results show that the HMG hydrogel has significant potential as a carrier for both charged hydrophilic drugs and hydrophobic drugs.

摘要

明胶分子已使用潜在细胞毒性试剂进行化学交联,以制备稳定的水凝胶。疏水相互作用是形成物理交联的一种手段,是在不使用细胞毒性化学物质的情况下提高明胶水凝胶稳定性的良好候选方法。在这项研究中,我们提出了一种使用高疏水性片段含量的疏水改性明胶(HMG)制备水凝胶的新方法。HMG 首先溶解在二甲基亚砜中,然后倒入具有所需形状的小瓶中。溶液冷冻干燥后,固体结构被水合。含有碱性成纤维细胞生长因子的 HMG 水凝胶在体内促进血管生成,表明带正电荷的亲水性生长因子与带负电荷的 HMG 水凝胶形成静电复合物,并随着水凝胶的降解在体内逐渐释放。此外,我们表明 HMG 的疏水片段通过疏水相互作用增强了模型疏水性治疗剂荧光素钠对水凝胶的吸附。此外,体外实验表明,疏水试剂将在体内以受控方式从水凝胶中释放。这些结果表明,HMG 水凝胶作为带电荷的亲水性药物和疏水性药物的载体具有很大的潜力。

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