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. 2016 Aug 30;32(34):8743-7.
doi: 10.1021/acs.langmuir.5b04755. Epub 2016 Aug 17.

Injectable and Glucose-Responsive Hydrogels Based on Boronic Acid-Glucose Complexation

Yizhou Dong  1 , Weiheng Wang  2   3 , Omid Veiseh  2   4   3 , Eric A Appel  2 , Kun Xue  2   5 , Matthew J Webber  2   3 , Benjamin C Tang  2   3 , Xi-Wen Yang  2 , Gordon C Weir  6 , Robert Langer  2   4   3   7 , Daniel G Anderson  2   4   3   7
Affiliations

Injectable and Glucose-Responsive Hydrogels Based on Boronic Acid-Glucose Complexation

Yizhou Dong et al. Langmuir. .

Abstract

Injectable hydrogels have been widely used for a number of biomedical applications. Here, we report a new strategy to form an injectable and glucose-responsive hydrogel using the boronic acid-glucose complexation. The ratio of boronic acid and glucose functional groups is critical for hydrogel formation. In our system, polymers with 10-60% boronic acid, with the balance being glucose-modified, are favorable to form hydrogels. These hydrogels are shear-thinning and self-healing, recovering from shear-induced flow to a gel state within seconds. More importantly, these polymers displayed glucose-responsive release of an encapsulated model drug. The hydrogel reported here is an injectable and glucose-responsive hydrogel constructed from the complexation of boronic acid and glucose within a single component polymeric material.

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Conflict of interest statement

Notes The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Design and synthesis of injectable hydrogel based on complexation between phenylboronic acid (PBA) and glucose. (A) PBA forms a five-membered ring in complex with diols such as glucose. (B) Illustration of PBA–glucose complexation on polymer chains. (C) Synthetic routes to polymer BG, which can self-assemble into an injectable and glucose-responsive hydrogel.
Figure 2
Figure 2
Hydrogels and their properties. (A) 5% polymer in water. Polymers BG 5–10 formed hydrogel in 5% water, while polymers BG 1–4 and 11 were in solid or liquid state in water. The control polymer BC-NH2 5 does not form a hydrogel. (B) Polymer BG 6 (50% PBA/50% glucose) is a soft and injectable hydrogel. (C) A cryo-SEM image of BG 6. Scale bar: 1 um.
Figure 3
Figure 3
Glucose responsiveness of BG6. (A) Strain dependence (ω = 10 rad/s) of the storage and loss moduli of BG6. (B) Frequency dependence (ε = 2%) of the storage and loss moduli of BG6. (C) Step–strain measurements of BG 6 to investigate the ability of the hydrogel to recover following deformation at high strains. This recovery occurs completely and rapidly, within seconds, indicative of shear-thinning and self-healing behaviors consistent with an injectable hydrogel. (D) Glucose responsiveness in vitro. BG 6 released a higher amount of rhodamine B in a 20 g/L solution than that in 1 g/L glucose and PBS only solutions. BG 6 (50% PBA/50% glucose).
See this image and copyright information in PMC

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