Glucose-Responsive Polymer Gel Bearing Phenylborate Derivative as a Glucose-Sensing Moiety Operating at the Physiological pH

Abstract

The work attempts to prepare a totally synthetic, glucose-responsive polymer gel bearing a phenylborate derivative as a sensor moiety to glucose, for future use as a self-regulated insulin delivery system. The molecular strategies to enable the system to be operated under physiological conditions (pH 7.4, 37 °C) are presented that involve the use of a novel phenylborate derivative {4-(1,6-dioxo-2,5-diaza-7-oxamyl) phenylboronic acid: DDOPBA} possessing an appreciably low pK a (∼7.8), the adoption of poly(Nisopropylmethacrylamide) (PNIPMAAm) for the main chain, which itself undergoes a sharp thermo-induced phase transition at its LCST around 40 °C, as well as the introduction of a carboxyl group of methacrylic acid as the third comonomer. Glucose-responsive behaviors of the obtained gels were evaluated based on the changes in the equilibrium swelling degree determined in the presence and the absence of glucose, for various pH and temperature conditions. As a consequence of the combined molecular effects, a sufficient sensitivity of the system was accomplished at physiological pH and in the temperature range close to the physiological condition such as 30 °C. Furthermore, the glucose-induced continuous volume changes of the gels were demonstrated under those conditions, which occurred in a remarkably concentration-dependent manner. In these experiments, the critical glucose concentrations to induce the gels' responses in the range of normoglycemic sugar level were observed. These observations may provide us with an excellent prospect for the use of the gel as a self-regulated, insulin-delivery system discretely switching the release at the normoglycemia.

Glucose-responsive polymer brushes for microcantilever sensing

“…latex 19 and polymer gels [20][21][22] has been demonstrated. Here we report the synthesis of glucose-responsive poly(N-isopropylacrylamide)-copoly(acrylic acid)-(3-aminophenyl-boronic acid) (PNIPAAM-co-PAA-PBA) brushes, and explore their potential for microcantilever based detection of glucose at physiologically relevant concentrations.…”

“…Soluble glucose binds to the tetrahedral, ionized boronate species within the brush and causes the observed additional swelling response. 17,20,21 Brush swelling due to the complexation of glucose is likely twofold: (i) the incorporation of a hydrophilic molecule and (ii) the increase in negative charge within the brush, which increases coulombic repulsive interactions, and osmotic pressure due to the increase in counterion concentration within the brush (see also below). These results confirm PBA's ability to complex glucose and cause conformational changes of PNIPAAM-co-PAA-PBA brushes.…”

Synthesis and properties of soft nanocomposite materials with novel organic/inorganic network structures

“…In particular, poly(N-isopropylacrylamide) (PNIPA), which undergoes a thermoresponsive coil-to-globule transition at a lower critical solution temperature (LCST E321C) in aqeous media, 14 is a typical example of a smart gel. To date, extensive studies have been conducted into the feasibility of using PNIPA hydrogels in various systems such as artificial insulin-control systems, 15 efficient bioseparation devices, 16 drug delivery systems 17 and biotechnological and tissue engineering devices. 18,19 Among the various types of polymer hydrogels, 'chemically crosslinked polymer hydrogels' have been widely used in academic studies as well as for practical applications, such as soft contact lenses and superabsorbent polymers, because their network composition and degree of crosslinking can be easily controlled.…”

“…[15][16][17][18][19] However, N-OR gels, consisting of chemically crosslinked networks, used so far had several important limitations, such as low volume change and slow deswelling rate, as well as poor mechanical properties. Among these disadvantages, slow rates of deswelling have been studied most extensively.…”

pH-Independent Recognition of Polyhydroxy Compounds by Niobium(V) Porphyrin Complex with Unique Sugar Selectivity

“…With a view to reducing the pH dependence of the reactivity, an electronwithdrawing substituent was proposed to increase the acidity of BA. 9,10 A special host containing two boronic acids or a supramolecular assembly system was proposed to enhance the selectivity to D-glucose. 6,7,[11][12][13] For further development towards various analytes, the hosts based on Lewis acids other than boron may be promising but have scarcely been explored; only Co(II) and Cu(II) complexes were examined for sugar sensing.…”