Clickable, acid labile immunosuppressive prodrugs for in vivo targeting

Hua Wang, Miguel C. Sobral, Tracy Snyder, Yevgeny Brudno, Vijay S. Gorantla, David J. Mooney

Research output: Contribution to journalArticlepeer-review

Abstract

Allotransplantation offers the potential to restore the anatomy and function of injured tissues and organs, but typically requires life-long, systemic administration of immunosuppressive drugs to prevent rejection, which can result in serious complications. Targeting the immunosuppressive drug to the graft favors local tissue concentration versus systemic drug exposure and end-organ toxicity. This could reduce the overall dose and dosing frequency of immunosuppressive drugs, and improve the safety and efficacy of treatment. Here, we developed dibenzocyclooctyne (DBCO)-modified prodrugs of the immunosuppressive drugs tacrolimus, rapamycin and mycophenolic acid, and demonstrated their targeted conjugation both in vitro and in vivo to azido-modified hydrogels via Click chemistry. Such azido-modified hydrogels placed in transplanted tissues enable sustained local release of drugs, and could be repeatedly refilled with systemically administered acid-labile prodrugs after drug exhaustion. Thus, clickable prodrugs with degradable linkers provide new possibilities for graft targeted immunosuppression in the context of allotransplantation.

Original languageEnglish (US)
Pages (from-to)266-277
Number of pages12
JournalBiomaterials Science
Volume8
Issue number1
DOIs
StatePublished - Jan 2020
Externally publishedYes

ASJC Scopus subject areas

  • Biomedical Engineering
  • Materials Science(all)

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