Reloadable multidrug capturing delivery system for targeted ischemic disease treatment

Jasmine P.J. Wu, Bill Cheng, Steve R. Roffler, David J. Lundy, Christopher Y.T. Yen, Peilin Chen, James J. Lai, Suzie H. Pun, Patrick S. Stayton, Patrick C.H. Hsieh

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

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 Mantibodies, 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.

Original languageEnglish
JournalScience Translational Medicine
Volume8
Issue number365
DOIs
Publication statusPublished - Nov 16 2016
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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