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

• Published in: International journal of biological macromolecules 2020-04, Vol.149, p.140-147
• Main Authors: Takei, Takayuki, Yoshihara, Ryosuke, Danjo, So, Fukuhara, Yoshiki, Evans, Courtney, Tomimatsu, Rio, Ohzuno, Yoshihiro, Yoshida, Masahiro
• Format: Article
• Language: English
• Subjects: Animals; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Drug Carriers - pharmacology; Fibroblast Growth Factor 2 - chemistry; Fibroblast Growth Factor 2 - pharmacokinetics; Fibroblast Growth Factor 2 - pharmacology; Fluorescein - chemistry; Fluorescein - pharmacokinetics; Fluorescein - pharmacology; Gelatin; Gelatin - chemistry; Gelatin - pharmacokinetics; Gelatin - pharmacology; Hydrogel; Hydrogels - chemistry; Hydrogels - pharmacokinetics; Hydrogels - pharmacology; Hydrophobic and Hydrophilic Interactions; Hydrophobic interaction; Male; Mice; Neovascularization, Physiologic - drug effects
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2020.01.227

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.