Release of functional dexamethasone by intracellular enzymes: A modular peptide-based strategy for ocular drug delivery

Madhushree Bhattacharya, Amir Sadeghi, Sanjay Sarkhel, Marja Hagström, Sina Bahrpeyma, Elisa Toropainen, Seppo Auriola, Arto Urtti

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Tissue barriers limit drug delivery in the eye. Therefore, retinal diseases are treated with intravitreal injections.
Delivery systems with reduced dosing frequency and/or cellular drug delivery properties are needed. We present
here a modular peptide-based delivery system for cell targeted release of dexamethasone in the retinal pigment
epithelial cells. The peptide–dexamethasone conjugates consist of cell penetrating peptide, enzyme cleavable
linker and dexamethasone that is conjugated with hydrazone bond. The conjugates are chemically stable in the
vitreous, internalize into the retinal pigment epithelial cells and release dexamethasone intracellularly by en-
zymatic action of cathepsin D. In vitro binding assay and molecular docking confirm binding of the released
dexamethasone fragment to the human glucocorticoid receptor. In vivo rabbit studies show increased vitreal
retention of dexamethasone with a peptide conjugate. Modular peptide conjugates are a promising approach for
drug delivery into the retinal cells.
Original languageEnglish
JournalJournal of Controlled Release
Volume327
Pages (from-to)584-594
Number of pages11
ISSN0168-3659
DOIs
Publication statusPublished - 10 Nov 2020
MoE publication typeA1 Journal article-refereed

Fields of Science

  • Conjugate
  • Dexamethasone
  • Drug delivery
  • INTRAVITREAL IMPLANT
  • Intravitreal
  • MACULAR DEGENERATION
  • NANOPARTICLES
  • PHARMACOKINETICS
  • PREDICTION
  • PROTEIN-BINDING
  • Peptide
  • Pharmacokinetics
  • RABBIT
  • RESIDENCE
  • Retinal pigment epithelium
  • SYSTEMS
  • TOXICITY
  • 317 Pharmacy

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