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

Hydrophobically-modified gelatin hydrogel as a carrier for charged hydrophilic drugs and hydrophobic drugs
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DOI:
10.1016/j.ijbiomac.2020.01.227
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发表时间:
2020-04-15
影响因子:
8.2
通讯作者:
Yoshida, Masahiro
Yoshida, Masahiro
中科院分区:
化学1区
文献类型:
--
作者:
Takei, Takayuki;Yoshihara, Ryosuke;Yoshida, Masahiro

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明胶分子已经使用潜在的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,这是在不使用细胞毒性化学品的情况下增强明胶水凝胶稳定性的良好候选物。在这项研究中,我们提出了一种新的方法,从疏水改性明胶(HMG)与高含量的疏水片段的水凝胶。首先将HMG溶解在二甲基亚砜中,并倒入具有所需形状的小瓶中。将溶液冷冻干燥后,将固体构建体水合。含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,我们发现,HMG的疏水部分增强了荧光素钠,疏水治疗剂的模型,通过疏水相互作用的水凝胶的吸附。此外,体外实验表明,疏水剂将在体内以受控的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显著的潜力。(C)2020 Elsevier B.V.保留所有权利。
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. (C) 2020 Elsevier B.V. All rights reserved.