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Review
. 2023 Jan 23;15(3):582.
doi: 10.3390/polym15030582.

Advances in the Design of Phenylboronic Acid-Based Glucose-Sensitive Hydrogels

Affiliations
Review

Advances in the Design of Phenylboronic Acid-Based Glucose-Sensitive Hydrogels

Simona Morariu. Polymers (Basel). .

Abstract

Diabetes, characterized by an uncontrolled blood glucose level, is the main cause of blindness, heart attack, stroke, and lower limb amputation. Glucose-sensitive hydrogels able to release hypoglycemic drugs (such as insulin) as a response to the increase of the glucose level are of interest for researchers, considering the large number of diabetes patients in the world (537 million in 2021, reported by the International Diabetes Federation). Considering the current growth, it is estimated that, up to 2045, the number of people with diabetes will increase to 783 million. The present work reviews the recent developments on the hydrogels based on phenylboronic acid and its derivatives, with sensitivity to glucose, which can be suitable candidates for the design of insulin delivery systems. After a brief presentation of the dynamic covalent bonds, the design of glucose-responsive hydrogels, the mechanism by which the hypoglycemic drug release is achieved, and their self-healing capacity are presented and discussed. Finally, the conclusions and the main aspects that should be addressed in future research are shown.

Keywords: dynamic covalent chemistry; glucose sensitivity; hydrogel; insulin releasing; phenylboronic acid; self-healing.

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Conflict of interest statement

The author declares no conflict of interest.

Figures

Figure 1
Figure 1
Physical and covalent bonds that provide the gels with self-healing ability.
Figure 2
Figure 2
Illustration of the main dynamic covalent bonds.
Figure 3
Figure 3
Configurations of PBA in water and complexation equilibrium between PBA-derivatives and glucose.
Figure 4
Figure 4
Preparation of poly(NIPAAm-co-APBA-co-AA) microcapsules (Adapted from reference [75] with permission from the Royal Society of Chemistry).
Figure 5
Figure 5
Volume changes of poly(NIPMAAm-co-AAmECFPBA) gel as a function of glucose amount at 37 °C (Adapted with permission from [77]. Copyright © 2023 WILEY-VCH Verlag GmbH & Co. KgaA, Weinheim, Germany).
Figure 6
Figure 6
Schematic illustration of poly(NIPAAm-co-DEX-co-DDOPBA) nanogel as insulin delivery system (Adapted with permission from [82]. Copyright © 2023 Elsevier Ltd. All rights reserved).
Figure 7
Figure 7
Structure of pH- and glucose-responsive CSPBA/PVA/OHC-PEG-CHO hydrogel (Adapted with permission from [83]. Copyright © 2023, American Chemical Society).
Figure 8
Figure 8
Schematic representation of the formation PEG-b-poly(AA-co-APBA/poly(AA-co-AGA micelles and their response in the glucose presence (Adapted with permission from [86]. Copyright © 2023, American Chemical Society).
Figure 9
Figure 9
Formation of glucose-responsiveness polymeric micelles based on two diblock copolymers which exhibit a reversible swelling in response to the change of glucose concentration and insulin protection under physiological conditions (Adapted from reference [90] with permission from the Royal Society of Chemistry).
Figure 10
Figure 10
Illustration of the preparation strategy of (PLys-Bor/Alg)n nanocapsules and the disassembly of the multilayers in the presence of glucose (Adapted with permission from [96]. Copyright © 2023 Elsevier Ltd. All rights reserved).
Figure 11
Figure 11
Elaboration of the glucose-responsive microcapsules based on AlgPBA and PVP (Adapted with permission from [97]. Copyright © 2023 Elsevier B.V. All rights reserved).
Figure 12
Figure 12
Illustration of SWCNTs preparation and glucose-sensitive complex formation. (Reprinted from reference [98] with permission from the Royal Society of Chemistry).
Figure 13
Figure 13
Preparation of microneedles by two-layer technique and their morphology determined at scale bar of 500 μm (Adapted with permission from [101]. Copyright © 2023, American Chemical Society).
Figure 14
Figure 14
Schematic illustration of DOP/PEI-PBA hydrogel as insulin delivery system (Adapted from reference [102]. Copyright © 2023 by Liu, W. et al.).
Figure 15
Figure 15
Preparation of PEG-DA/CS-GA/PEI-PBA hydrogel loaded with insulin nanoparticles (NPs) and its mechanism of glucose level regulation (Adapted with permission from [103]. Copyright © 2023, Tsinghua University Press).
Figure 16
Figure 16
Schematic representation of polymer-insulin complex formation and of insulin release from complex under a hyperglycemic condition (Adapted from reference [104]. Copyright © 2023 by Wang, J. et al.).
Figure 17
Figure 17
(a) Shear-thinning behavior and (b) exemplification of the self-healing property of the gel based on PEG and 3-fluorophenylboronic acid formed at pH = 7 (Reproduced with permission from [106]. Copyright © 2023 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).
Figure 18
Figure 18
Illustration of (a) alternate-step strain test and (b) injection and self-healing phenomenon of the hydrogel based on 4-carboxy-3-fluorophenylboronic grafted chitooligosaccharides and guar gum (Adapted with permission from [112]. Copyright © 2023 Wiley-VCH GmbH).

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