A Dual Stimuli Responsive Supramolecular Gel Provides Insulin Hydrolysis Protection and Redox‐Controlled Release of Actives

Abstract

Two supramolecular hydrogelators containing a central disulfide moiety and terminal carboxylic acid groups are studied. On the one hand, the hydrogels are responsive to a reductive environment, which transforms the disulfide unit to the corresponding thiols. On the other hand, the hydrogels show pH response associated with the presence of carboxylic acid units. Gels are formed at pH below ≈4 while at higher pH values, ionization of the gelators provokes gel disassembly. The properties of the gel are exploited for the release, as a proof of concept, of Bromophenol Blue in the presence of the reducing species tris(2‐carboxyethyl)phosphine hydrochloride. Additionally, insulin is loaded into the hydrogels and protected from hydrolysis with simulated gastric fluid containing pepsin. Quantitative release of unaltered insulin, checked with an enzyme‐linked immunosorbent assay colorimetric assay, is observed upon treatment with pH 7.4 buffer. This behavior would permit the use of the new hydrogels for oral insulin delivery.

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“…Supramolecular gels − are an important class of materials because of their potential applications such as in catalysis, − conservation of arts, light-harvesting materials, conducting materials, ,, sensing, − drug delivery, − self-drug delivery, − tissue engineering, − and so forth. Gels are formed from a solution or a suspension containing a solid (gelator) usually by a heating–cooling (to room temperature) process.…”

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“…The insulin loaded into the gels prevented its degradation in the pepsin‐containing simulated gastric fluid, where the fibrillar gel network guards insulin and regulates pectin's diffusion to the gel (pectin hydrolyses free insulin instantaneously). Altering acidic pH to neutral pH 7.4 caused gelator solubilization and insulin release [111] . Kumar et al.…”

“…Altering acidic pH to neutral pH 7.4 caused gelator solubilization and insulin release. [111] Kumar et al reported enzymatically cleavable and pH-responsive hydrogels based on phenoxy-alkyl maleate-based amphiphiles where the entrapped hydrophobic drug was released via the enzyme-assisted hydrolysis of the ester bond. Moreover, the curcumin-trapped [106] Reproduced with permission from [106] © 2019 American Chemical Society.…”