Drug-peptide supramolecular hydrogel boosting transcorneal permeability and pharmacological activity via ligand-receptor interaction

Lin Chen, Jie Deng, Ailing Yu, Yuhan Hu, Bo Jin, Pengyuan Du, Jianhong Zhou, Lei Lei, Yuan Wang, Serhii Vakal, Xingyi Li

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Boosting transcorneal permeability and pharmacological activity of drug poses a great challenge in the field of ocular drug delivery. In the present study, we propose a drug-peptide supramolecular hydrogel based on anti-inflammatory drug, dexamethasone (Dex), and Arg-Gly-Asp (RGD) motif for boosting transcorneal permeability and pharmacological activity via the ligand-receptor interaction. The drug-peptide (Dex-SA-RGD/RGE) supramolecular hydrogel comprised of uniform nanotube architecture formed spontaneously in phosphate buffered saline (PBS, pH = 7.4) without external stimuli. Upon storage at 4 °C, 25 °C, and 37 °C for 70 days, Dex-SA-RGD in hydrogel did not undergo significant hydrolysis, suggesting great long-term stability. In comparison to Dex-SA-RGE, Dex-SA-RGD exhibited a more potent in vitro anti-inflammatory efficacy in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages via the inhibition of nuclear factor кB (NF-κB) signal pathway. More importantly, using drug-peptide supramolecular hydrogel labeled with 7-nitro-2,1,3-benzoxadiazole (NBD), the Dex-SA-K(NBD)RGD showed increased performance in terms of integrin targeting and cellular uptake compared to Dex-SA-K(NBD)RGE, as revealed by cellular uptake assay. On topical instillation in rabbit's eye, the proposed Dex-SA-K(NBD)RGD could effectively enhance the transcorneal distribution and permeability with respect to the Dex-SA-K(NBD)RGE. Overall, our findings demonstrate the performance of the ligand-receptor interaction for boosting transcorneal permeability and pharmacological activity of drug.
Original languageEnglish
JournalBioactive materials
DOIs
Publication statusPublished - Sep 2021
MoE publication typeA1 Journal article-refereed

Keywords

  • Active transport, Integrin, Supramolecular hydrogel, Ocular retention, Corneal permeability

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