A self-assembling peptide hydrogel-based drug co-delivery platform to improve tissue repair after ischemia-reperfusion injury
| Autor: | Meng Zhao, Jingping Liu, Younan Chen, Ling Li, Yujia Yuan, William Bresette, Yanrong Lu, Guangneng Liao, Chengshi Wang, Yijie Zhou, Lan Li, Jingqiu Cheng, Shuyun Liu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0206 medical engineering Biomedical Engineering Inflammation 02 engineering and technology Pharmacology Biochemistry Injections Biomaterials Drug Delivery Systems In vivo medicine Renal fibrosis Animals Regeneration Amino Acid Sequence Molecular Biology Wound Healing Heparin Hepatocyte Growth Factor Tumor Necrosis Factor-alpha business.industry Regeneration (biology) Hydrogels General Medicine Acute Kidney Injury 021001 nanoscience & nanotechnology medicine.disease Fibrosis 020601 biomedical engineering Controlled release Mice Inbred C57BL Drug Liberation Reperfusion Injury Systemic administration Hepatocyte growth factor medicine.symptom Peptides 0210 nano-technology business Reperfusion injury Biotechnology medicine.drug |
| Zdroj: | Acta Biomaterialia. 103:102-114 |
| ISSN: | 1742-7061 |
| DOI: | 10.1016/j.actbio.2019.12.011 |
| Popis: | Ischemia-reperfusion (I/R)-induced organ injury is a serious health problem worldwide, and poor recovery of acute phase injury leads to chronic fibrosis and further organ dysfunction. Thus, a more precise approach to enhance tissue repair is needed. By using a renal I/R model, we aimed to evaluate the role of a hydrogel-based dual-drug delivery platform on promoting tissue repair. An injectable, self-assembling peptide/heparin (SAP/Hep) hydrogel was used to co-deliver TNF-α neutralizing antibody (anti-TNF-α) and hepatocyte growth factor (HGF). The microstructure and controlled release properties of KLD2R/Hep hydrogel were analyzed. The effects of the drug-loaded hydrogel (SAP-drug) on renal injury were evaluated in mice with I/R injury. In vitro, the SAP/Hep hydrogel allowed for a faster release of anti-TNF-α with a sustained release of HGF, and both drugs maintained their bioactivities after release. In vivo, combined anti-TNF-α/HGF showed better renal protective potential than anti-TNF-α or HGF alone. SAP-drug (anti-TNF-α/HGF in SAP hydrogel) treatment reduced the level of serum creatinine (Scr), blood urea nitrogen (BUN), tubular apoptosis, renal inflammatory factors, and macrophage infiltration compared to Free-drug (anti-TNF-α/HGF in solution) or SAP alone. Moreover, the SAP-drug group had better efficacy on promoting tubular cell proliferation and dedifferentiation than SAP or Free-drug alone, and thus reduced chronic renal fibrosis in I/R mice. This study highlighted that SAP could sequentially deliver the two drugs to achieve anti-inflammatory and pro-proliferative effects with one injection and thus is a promising delivery platform for tissue repair. STATEMENT OF SIGNIFICANCE: Ischemia-reperfusion (I/R)-induced organ injury is a serious health issue, and delayed tissue repair leads to chronic fibrosis and organ failure. Systemic administration of anti-inflammatory agents or growth factors have shown some benefits on I/R injury, but their therapeutic efficacy was limited by side effects, poor bioavailability, and absent key signals of tissue repair. To address these issues, a hydrogel-based drug co-delivery platform was used to treat I/R injury. This platform could achieve sequential release kinetics with faster rate of anti-TNF-ɑ and slower rate of HGF, and effectively promoted tissue repair by targeting inflammation and proliferation in mice with renal I/R. This nanoscale delivery platform represents a promising strategy for solid organs (heart, liver and kidney) regeneration after I/R. |
| Databáze: | OpenAIRE |
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