Biofunctionalization of nanoceria with sperminated hyaluronan enhances drug delivery performance for corneal alkali burn therapy

Tzong Yun Ger, Chia Jung Yang, Sandip Ghosh, Jui Yang Lai*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

12 Scopus citations

Abstract

Corneal alkali burn (AB) injury is the most common sight-threatening injury that is highly associated with oxidative stress, inflammation, apoptosis, angiogenesis, and cell deficiency. Most therapeutic options are ineffective in improving and reversing pathological conditions. This study aims to develop a delivery system based on sperminated hyaluronan (sH)-functionalized nanoceria (Ce-sH nanoparticles (NPs)) with enhanced barrier penetration capability and increased ocular drug bioavailability. The functional surface properties and therapeutic bioactivities of Ce-sH NPs were evaluated. We observed a high tight-junction opening capacity with higher spermine content, resulting in excellent permeability and cellular uptake efficiency (fourfold that of bare Ce NPs). The NPs exhibited high drug (insulin-like growth factor 1, IGF-1) entrapment efficiency (10-fold) and hyaluronidase-triggered controlled slow release (up to 168 h) compared with bare Ce NPs. The IGF-1-loaded Ce-hsH NPs (I@Ce-hsH) had the best wound healing rate (>90 %). In contrast to a clinically used eye drop (dexamethasone), the I@Ce-hsH significantly reduced corneal defects to <1 % and restored the tissue transparency to a normal range within 7 d post-instillation in a rat model of AB. In summary, our bioactive nanoformulations successfully reversed corneal injury and has great potential in the design of biomaterials for ocular therapeutics.

Original languageEnglish
Article number146864
JournalChemical Engineering Journal
Volume476
DOIs
StatePublished - 15 11 2023

Bibliographical note

Publisher Copyright:
© 2023 Elsevier B.V.

Keywords

  • Corneal alkali burn
  • Hyaluronan
  • IGF-1
  • Nanoceria
  • Spermine

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