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...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℃,25℃,and 37℃ 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 factorкB(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.展开更多
基金supported by the Zhejiang Provincial Natural Science Foundation of China(Grant No.LR18H300002 and LQ20C080002)the National Natural Science Foundation of China(Grant No.81971732).
文摘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℃,25℃,and 37℃ 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 factorкB(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.
