Phenylboronic Acid Appended Pyrene‐Based Low‐Molecular‐Weight Injectable Hydrogel: Glucose‐Stimulated Insulin Release

Abstract

A pyrene-containing phenylboronic acid (PBA) functionalized low-molecular-weight hydrogelator was synthesized with the aim to develop glucose-sensitive insulin release. The gelator showed the solvent imbibing ability in aqueous buffer solutions of pH values, ranging from 8-12, whereas the sodium salt of the gelator formed a hydrogel at physiological pH 7.4 with a minimum gelation concentration (MGC) of 5 mg mL(-1) . The aggregation behavior of this thermoreversible hydrogel was studied by using microscopic and spectroscopic techniques, including transmission electron microscopy, FTIR, UV/Vis, luminescence, and CD spectroscopy. These investigations revealed that hydrogen bonding, π-π stacking, and van der Waals interactions are the key factors for the self-assembled gelation. The diol-sensitive PBA part and the pyrene unit in the gelator were judiciously used in fluorimetric sensing of minute amounts of glucose at physiological pH. The morphological change of the gel due to addition of glucose was investigated by scanning electron microscopy, which denoted the glucose-responsive swelling of the hydrogel. A rheological study indicated the loss of the rigidity of the native gel in the presence of glucose. Hence, the glucose-induced swelling of the hydrogel was exploited in the controlled release of insulin from the hydrogel. The insulin-loaded hydrogel showed thixotropic self-recovery property, which hoisted it as an injectable soft composite. Encouragingly, the gelator was found to be compatible with HeLa cells.

Hydrophobic End‐Modulated Amino‐Acid‐Based Neutral Hydrogelators: Structure‐Specific Inclusion of Carbon Nanomaterials

“…Amphiphile 4 was found to gelate in water with improved efficiency (MGC=10 mg mL −1 ). The decrease in MGC compared with 1 and 3 , (which gelate in pure water) is probably caused by the additional π–π stacking interaction between pyrenyl moieties . We also monitored the gelation abilities of 1 – 4 in phosphate‐HCl buffer of pH 3.0–7.0 (Table ).…”

“…Simultaneously with rapid structural advancement, researchers are trying to build up soft nanocomposites composed of nanomaterial‐integrated gel, with the objective of improving its physicochemical properties. Hybrid gels (containing nanomaterials) with improved mechanical stiffness are finding applications in the area of supercapacitors, nanoelectronics, photovoltaic devices, chemical sensors, biomedicine, and so on . Exogenous nanomaterials such as carbon nanotubes (CNTs), graphene, graphene oxide (GO), silver nanoparticles, gold nanoparticles, and so on, have been included in the interstitial spaces of SAFINs, and aided advantageous changes in their properties .…”

Polypeptide-participating complex nanoparticles with improved salt-tolerance as excellent candidates for intelligent insulin delivery

“…[3][4][5] Amongst these self-regulated insulin delivery systems, synthetic phenylboronic acid (PBA)-based polymeric materials with high stability have shown more promising applications than glucose oxidase (GOD) and lectin (Con A) based systems. [6][7][8] Until now, a variety of PBA-based glucose-responsive materials particularly in the form of nanoparticles including nanogels (microgels), [9][10][11] micelles, [12][13][14][15] vesicles, [16][17][18][19][20] and mesoporous silica nanoparticles 21,22 have been broadly explored and shown to exhibit effective glucose-responsiveness at physiological pH and reasonable glucose-sensitivity.…”

Biologically Inspired and Chemically Derived Methods for Glucose‐Responsive Insulin Therapy

“…To address this challenge, the p K a of PBAs has been varied through the inclusion of adjacent functional groups that typically serve to promote the anionic tetrahedral geometry, either through additional covalent bonding directly to the boron atom or by inclusion of electron‐withdrawing substituents on the aryl ring . These efforts have been sufficient to shift the effective p K a of different PBA moieties to near‐physiological levels, or even significantly lower in some cases, thereby enabling functional operation of these groups in relevant conditions (Figure B) …”