Esterase-Mediated Sustained Release of Peptide-Based Therapeutics from a Self-Assembled Injectable Hydrogel

Ketav Kulkarni, Rachel L. Minehan, Tanesh Gamot, Harold A. Coleman, Simon Bowles, Qingqing Lin, Denham Hopper, Susan E. Northfield, Richard A. Hughes, Robert E. Widdop, Marie Isabel Aguilar, Helena C. Parkington, Mark P. Del Borgo

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)

Abstract

A synthetic strategy for conjugating small molecules and peptide-based therapeutics, via a cleavable ester bond, to a lipidated β3-tripeptide is presented. The drug-loaded β3-peptide was successfully co-assembled with a functionally inert lipidated β3-tripeptide to form a hydrogel. Quantitative release of lactose from the hydrogel, by the action of serum esterases, is demonstrated over 28 days. The esterase-mediated sustained release of the bioactive brain-derived neurotrophic factor (BDNF) peptide mimics from the hydrogel resulted in increased neuronal survival and normal neuronal function of peripheral neurons. These studies define a versatile strategy for the facile synthesis and co-assembly of self-assembling β3-peptide-based hydrogels with the ability to control drug release using endogenous esterases with potential in vivo applications for sustained localized drug delivery.

Original languageEnglish
Pages (from-to)58279-58290
Number of pages12
JournalACS Applied Materials & Interfaces
Volume13
Issue number49
DOIs
Publication statusPublished - 15 Dec 2021

Keywords

  • esterase-mediated controlled release
  • injectable materials
  • peptide-based hydrogels
  • supramolecular self-assembly
  • sustained drug delivery

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