期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 8, 期 365, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aah6228
关键词
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资金
- National Research Program for Biopharmaceuticals of the Ministry of Science and Technology (MOST) [102-2321-B-001-069, 104-2325-B-001-010]
- Ministry of Health and Welfare [104TM1001]
- Academia Sinica Translational Medicine Program
- Academia Sinica Nanoscience and Nanotechnology Program, Taiwan
Human clinical trials of protein therapy for ischemic diseases have shown disappointing outcomes so far, mainly because of the poor circulatory half-life of growth factors in circulation and their low uptake and retention by the targeted injury site. The attachment of polyethylene glycol (PEG) extends the circulatory half-lives of protein drugs but reduces their extravasation and retention at the target site. To address this issue, we have developed a drug capture system using a mixture of hyaluronic acid (HA) hydrogel and anti-PEG immunoglobulin M antibodies, which, when injected at a target body site, can capture and retain a variety of systemically injected PEGylated therapeutics at that site. Furthermore, repeated systemic injections permit reloading of the capture depot, allowing the use of complex multistage therapies. This study demonstrates this capture system in both murine and porcine models of critical limb ischemia. The results show that the reloadable HA/anti-PEG system has the potential to be clinically applied to patients with ischemic diseases, who require sequential administration of protein drugs for optimal outcomes.
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