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

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.

Multifunctional Supramolecular Filament Hydrogel Boosts Anti‐Inflammatory Efficacy In Vitro and In Vivo

“…[ 36 ] The conjugation of dexamethasone and Arg‐Gly‐Asp (i.e., RGD) generates a PDC supramolecular hydrogel, which boosts the transcorneal permeability and pharmacological activity via the ligand‐receptor interaction. [ 37,38 ]…”

“…[36] The conjugation of dexamethasone and Arg-Gly-Asp (i.e., RGD) generates a PDC supramolecular hydrogel, which boosts the transcorneal permeability and pharmacological activity via the ligand-receptor interaction. [37,38] Inspired by these studies, we integrated a polyphenol, a non-steroidal anti-inflammatory drug and a self-assembled peptide motif to generate a PDCs (2IPF-DHB-GFFYD), which could self-assemble into supramolecular hydrogel to exert the synergistic effects and consequently higher therapeutic efficacy. The principles of our design are described as follows: 1) Non-steroidal anti-inflammatory drug (NSAID), ibuprofen (IPF), was selected as the capping group; 2) Polyphenol, 3,5-Dihydroxybenzoic acid (DHB) acting as an antioxidant, was used as the linker between IPF and the peptide sequence; 3) The labile ester bond bridge between IPF and DHB enables both of two therapeutic agents to transform into active forms upon hydrolysis; 4) Dipeptide of phenylalanine (F), widely used as the hydrogelator motif, facilitates the self-assembly of molecules; 5) The aspartic acid (D) balances the hydrophobicity and hydrophilicity of hydrogelator, and also stabilizes the resulting supramolecular hydrogel.…”

Nanocarrier‐embedded gels: Precision drug delivery via liposomal and niosomal platforms

“…This formulation enhances transcorneal permeability, thereby facilitating the treatment of ocular inflammation. 25 An alternative methodology for triggering the activation of gels involves the utilization of light stimuli. This class of gels undergoes a transformation in its conformation, transitioning from a sol to gel state in response to irradiation or exposure to visible light sources.…”

A New Approach to Supramolecular Structure Determination in Pharmaceutical Preparation of Self-Assembling Peptides: A Case Study of Lanreotide Autogel

“…Some peptide sequences include amino acid sequences that spontaneously generate supramolecular-ordered aggregates. These, through noncovalent intermolecular interactions, maintain the peptide-based self-assembled structures in a stable low-energy state [ 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. Self-assembled supramolecular structures, depending on their morphology, exert different physicochemical and biological properties; therefore, they are widely studied as the basis of many neurodegenerative diseases and can be used for intracellular or targeted tissue drug delivery.…”

“…They are also extensively studied for the prolonged release of peptide drugs, which can deliver monomers in a controlled manner. In this context, the study of proteins and peptide self-association and the parameters that can influence these processes paves the path for a wide range of applications [ 34 , 35 , 36 , 37 , 38 , 39 , 40 ].…”