Directed self-assembly of herbal small molecules into sustained release hydrogels for treating neural inflammation

• Published in: Nature communications 2019-04, Vol.10 (1), p.1604-1604, Article 1604
• Main Authors: Zheng, Jun, Fan, Rong, Wu, Huiqiong, Yao, Honghui, Yan, Yujie, Liu, Jiamiao, Ran, Lu, Sun, Zhifang, Yi, Lunzhao, Dang, Li, Gan, Pingping, Zheng, Piao, Yang, Tilong, Zhang, Yi, Tang, Tao, Wang, Yang
• Format: Article
• Language: English
• Subjects: 140/58; 147/135; 147/143; 631/61/54/152; 631/61/54/990; 639/638/298/923/1027; 639/638/298/923/966; 639/638/92/613; 96/95; Animals; Anthraquinones - administration & dosage; Anthraquinones - chemistry; Anthraquinones - pharmacokinetics; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacokinetics; Assembling; Biocompatibility; Biomedical materials; Cell Line; Controlled release; Cytotoxicity; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacokinetics; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Drug Evaluation, Preclinical; Drug Liberation; Gels; Humanities and Social Sciences; Hydrogels; Hydrogels - administration & dosage; Hydrogels - chemistry; Hydrogels - pharmacokinetics; Inflammation; Inflammation - drug therapy; Inflammation - immunology; Inflammation - pathology; Lipopolysaccharides; Lipopolysaccharides - immunology; Mice; Microglia; Microglia - drug effects; Microglia - immunology; Microglia - pathology; Microscopy, Electron, Scanning; multidisciplinary; Nanofibers; Nanofibers - administration & dosage; Nanofibers - chemistry; Nanofibers - ultrastructure; Natural products; NF-KappaB Inhibitor alpha - immunology; NF-KappaB Inhibitor alpha - metabolism; NF-κB protein; Nuclear transport; Phosphorylation - drug effects; Phosphorylation - immunology; Phytochemicals - administration & dosage; Phytochemicals - chemistry; Phytochemicals - pharmacokinetics; Rheum - chemistry; Science; Science (multidisciplinary); Self-assembly; Signal transduction; Signal Transduction - drug effects; Signal Transduction - immunology; Sustained release; TLR4 protein; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Toxicity; Transcription Factor RelA - immunology; Transcription Factor RelA - metabolism; Translocation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-09601-3

Self-assembling natural drug hydrogels formed without structural modification and able to act as carriers are of interest for biomedical applications. A lack of knowledge about natural drug gels limits there current application. Here, we report on rhein, a herbal natural product, which is directly self-assembled into hydrogels through noncovalent interactions. This hydrogel shows excellent stability, sustained release and reversible stimuli-responses. The hydrogel consists of a three-dimensional nanofiber network that prevents premature degradation. Moreover, it easily enters cells and binds to toll-like receptor 4. This enables rhein hydrogels to significantly dephosphorylate IκBα, inhibiting the nuclear translocation of p65 at the NFκB signalling pathway in lipopolysaccharide-induced BV2 microglia. Subsequently, rhein hydrogels alleviate neuroinflammation with a long-lasting effect and little cytotoxicity compared to the equivalent free-drug in vitro. This study highlights a direct self-assembly hydrogel from natural small molecule as a promising neuroinflammatory therapy. There is interest in the development of drug-based hydrogels for responsive sustained drug release. Here, the authors report on the self-assembly of natural small molecule, rhein, into hydrogels and the application of the hydrogels as stable controlled release agents for neuro-inflammatory therapy