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

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...

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Autores principales:	Lin Chen, Jie Deng, Ailing Yu, Yuhan Hu, Bo Jin, Pengyuan Du, Jianhong Zhou, Lei Lei, Yuan Wang, Serhii Vakal, Xingyi Li
Formato:	article
Lenguaje:	EN
Publicado:	KeAi Communications Co., Ltd. 2022
Materias:	Active transport Integrin Supramolecular hydrogel Ocular retention Corneal permeability Materials of engineering and construction. Mechanics of materials TA401-492 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0ae567cf3ca14845872684223abbbabd
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spelling	oai:doaj.org-article:0ae567cf3ca14845872684223abbbabd2021-11-28T04:35:30ZDrug-peptide supramolecular hydrogel boosting transcorneal permeability and pharmacological activity via ligand-receptor interaction2452-199X10.1016/j.bioactmat.2021.09.006https://doaj.org/article/0ae567cf3ca14845872684223abbbabd2022-04-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2452199X21004163https://doaj.org/toc/2452-199XBoosting 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.Lin ChenJie DengAiling YuYuhan HuBo JinPengyuan DuJianhong ZhouLei LeiYuan WangSerhii VakalXingyi LiKeAi Communications Co., Ltd.articleActive transportIntegrinSupramolecular hydrogelOcular retentionCorneal permeabilityMaterials of engineering and construction. Mechanics of materialsTA401-492Biology (General)QH301-705.5ENBioactive Materials, Vol 10, Iss , Pp 420-429 (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Active transport Integrin Supramolecular hydrogel Ocular retention Corneal permeability Materials of engineering and construction. Mechanics of materials TA401-492 Biology (General) QH301-705.5
spellingShingle	Active transport Integrin Supramolecular hydrogel Ocular retention Corneal permeability Materials of engineering and construction. Mechanics of materials TA401-492 Biology (General) QH301-705.5 Lin Chen Jie Deng Ailing Yu Yuhan Hu Bo Jin Pengyuan Du Jianhong Zhou Lei Lei Yuan Wang Serhii Vakal Xingyi Li Drug-peptide supramolecular hydrogel boosting transcorneal permeability and pharmacological activity via ligand-receptor interaction
description	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.
format	article
author	Lin Chen Jie Deng Ailing Yu Yuhan Hu Bo Jin Pengyuan Du Jianhong Zhou Lei Lei Yuan Wang Serhii Vakal Xingyi Li
author_facet	Lin Chen Jie Deng Ailing Yu Yuhan Hu Bo Jin Pengyuan Du Jianhong Zhou Lei Lei Yuan Wang Serhii Vakal Xingyi Li
author_sort	Lin Chen
title	Drug-peptide supramolecular hydrogel boosting transcorneal permeability and pharmacological activity via ligand-receptor interaction
title_short	Drug-peptide supramolecular hydrogel boosting transcorneal permeability and pharmacological activity via ligand-receptor interaction
title_full	Drug-peptide supramolecular hydrogel boosting transcorneal permeability and pharmacological activity via ligand-receptor interaction
title_fullStr	Drug-peptide supramolecular hydrogel boosting transcorneal permeability and pharmacological activity via ligand-receptor interaction
title_full_unstemmed	Drug-peptide supramolecular hydrogel boosting transcorneal permeability and pharmacological activity via ligand-receptor interaction
title_sort	drug-peptide supramolecular hydrogel boosting transcorneal permeability and pharmacological activity via ligand-receptor interaction
publisher	KeAi Communications Co., Ltd.
publishDate	2022
url	https://doaj.org/article/0ae567cf3ca14845872684223abbbabd
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Drug-peptide supramolecular hydrogel boosting transcorneal permeability and pharmacological activity via ligand-receptor interaction

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