Glucose-Sensitive Polyphosphoester Diblock Copolymer for an Insulin Delivery System

Li, Hongping; He, Jinlin; Zhang, Mingzu; Liu, Jian; Ni, Peihong

doi:10.1021/acsbiomaterials.9b01817

Cited by 16 publications

(8 citation statements)

References 68 publications

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“…According to the previous in vitro enzymatic degradation experiments of the main chain PBYP-b-PEEP characterized by 1 H NMR by our group, it can be concluded that PBYP-b-PEEP has favorable biodegradability. 51,52 Therefore, the prepared CCL NPs have the potential to release insulin in response to different glucose concentrations to reduce blood glucose.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Glucose-Sensitive Core-Cross-Linked Nanoparticles Constructed with Polyphosphoester Diblock Copolymer for Controlling Insulin Delivery

Zhou

et al. 2021

Bioconjugate Chem.

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This work aims to construct biocompatible, biodegradable core-cross-linked and insulin-loaded nanoparticles which are sensitive to glucose and release insulin via cleavage of the nanoparticles in a high-concentration blood glucose environment. First, a polyphosphoester-based diblock copolymer (PBYP-g-Gluc)-b-PEEP was prepared via ring-opening copolymerization (ROP) and the copper(I)-catalyzed azide−alkyne cycloaddition (CuAAC) in which PBYP and PEEP represent the polymer segments from 2-(but-3-yn-1-yloxy)-2-oxo-1,3,2-dioxaphospholane and 2-ethoxy-2-oxo-1,3,2-dioxaphospholane, respectively, and Gluc comes from 2azidoethyl-β-D-glucopyranoside (Gluc-N 3 ) that grafted with PBYP. The structure and molecular weight of the copolymer were characterized by 1 H NMR, 31 P NMR, GPC, FT-IR, and UV−vis measurements. The amphiphilic copolymer could self-assemble into core−shell uncore-cross-linked nanoparticles (UCCL NPs) in aqueous solutions and form core-cross-linked nanoparticles (CCL NPs) after adding cross-linking agent adipoylamidophenylboronic acid (AAPBA). Dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to study the self-assembly behavior of the two kinds of NPs and the effect of different Gluc group contents on the size of NPs further to verify the stability and glucose sensitivity of CCL NPs. The ability of NPs to load fluorescein isothiocyanate-labeled insulin (FITC−insulin) and their glucose-triggered release behavior were detected by a fluorescence spectrophotometer. The results of methyl thiazolyl tetrazolium (MTT) assay and hemolysis activity experiments showed that the CCL NPs had good biocompatibility. An in vivo hypoglycemic study has shown that FITC−insulin-loaded CCL NPs could reduce blood glucose and have a protective effect on hypoglycemia. This research provides a new method for constructing biodegradable and glucose-sensitive core-cross-linked nanomedicine carriers for controlled insulin release.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Glucose-Sensitive Core-Cross-Linked Nanoparticles Constructed with Polyphosphoester Diblock Copolymer for Controlling Insulin Delivery

Zhou

et al. 2021

Bioconjugate Chem.

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“…Ni and co‐workers developed a glucose responsive insulin delivery system based on diblock polyphosphoester grafted with boronic acid units. [ 129 ] The authors reasoned that the advantages of polyphosphoesters, such as biocompatibility, biodegradability, facile synthesis and functionalisation at low cost, make polyphosphoesters ideal candidates for creating insulin‐release platforms. [ 130 ] Preparation of their final material consisted of three steps, the first being ring opening polymerisation leading to a diblock polyphosphoester, this was followed by double ( click ) reaction of 3‐mercaptopropionic acid ( 28 ) with an alkyne, the free carboxylic acid groups of which were amide‐coupled with 24 ( Scheme ).…”

Section: Nanoparticlesmentioning

confidence: 99%

“…The synthetic route toward the diblock polyphosphoester based glucose responsive insulin delivery system reported by Ni and co‐workers. [ 129 ] Ring opening polymerisation yielded the diblock polyphosphoester (PBYP‐ b ‐PEEP) , which was subsequently thiolated with 28 giving (PBYP‐ g ‐MPA)‐ b ‐MEEP . To imbue the material with glucose responsivity, 3‐aminophenylboronic acid 24 was bound through amide coupling to the free acid groups to yield (PBYP‐ g ‐MPBA)‐ b‐ PEEP .…”

Section: Nanoparticlesmentioning

confidence: 99%

Insulin Delivery Using Dynamic Covalent Boronic Acid/Ester‐Controlled Release

Banach

Williams

Fossey

2021

Advanced Therapeutics

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The number of people affected by diabetes mellitus increases globally year on year. Elevated blood glucose levels may result from a lack of insulin to manage these levels and can, over a prolonged period, lead to serious repercussions. Diabetes mellitus patients must monitor and control their blood‐glucose levels with invasive testing and often alongside administration of intravenous doses of insulin, which can often lead to suboptimal compliance. To mitigate these issues, “closed‐loop” insulin delivery systems are deemed to be among superior options for rapid relief from the demanding and troublesome necessity of self‐directed care. The reversible dynamic covalent chemistry of boronic acid derivatives and their competitive affinity to 1,2‐ and 1,3‐diols (such as those present in saccharides) allows for the design and preparation of responsive self‐regulated insulin delivery materials which respond to elevated and changing glucose levels. A range of meritorious and noteworthy contributions in the domain of boron‐mediated insulin delivery materials is surveyed, and providing a multidisciplinary context in the realisation of the ambitious goal of ultimately addressing the desire to furnish glucose‐responsive insulin delivery materials through innovative synthesis and rigorous testing is targetted.

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“…This observation is in line with relevant research reports. 37,38 For example, Li et al 39 produced a diblock copolymer based on a polyphosphate backbone and pendant phenylboronic acid (PBYP-g-MPBA)-b-PEEP. They found that the size of the NPs particle was not significantly affected over 7 days.…”

Section: Glucose Sensitivity Of P(aapba-co-pte) Nanoparticlesmentioning

confidence: 99%

Nanoparticles capable of managing hypoglycemia and preventing myocardial ischemia‐reperfusion injury

Bian

Xiao-min

et al. 2021

J of Applied Polymer Sci

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Diabetes, and its complications, is a major threat to human health. In this research, we successfully synthesized a new type of glucose-responsive poly (3-acrylamidophenylboronic acid-co-pterostilbene) (p(AAPBA-co-PTE) nanoparticle. The nanoparticles are round in shape with a size between 150 and 200 nm. Insulin-loaded p(AAPBA-co-PTE) nanoparticles can self-adjust according to the changes in glucose concentration in vitro to achieve effective and sustained levels of insulin. P(AAPBA-co-PTE) nanoparticles have good stability, and the drug loading of insulin-loaded p(AAPBA-co-PTE) nanoparticles is up to 16.7%, the encapsulation efficiency is up to 82.4% and the release rate of pterostilbene in vitro is up to 81%. The p(AAPBA-co-PTE) nanoparticles have low toxicity toward cells, and can effectively reduce blood sugar within 24 h. After 14 days of treatment, an animal model of myocardial ischemiareperfusion injury (MI/RI) was established. After treatment with the insulin-loaded p(AAPBA-co-PTE) nanoparticles, the rat heart function was significantly improved, and the levels of inflammatory factors were significantly reduced. P(AAPBA-co-PTE) nanoparticles were therefore successfully synthesized, and had good performance. P(AAPBA-co-PTE) nanoparticles appear to have the effect of reducing blood sugar and preventing MI/RI, and may be valuable for the development of treatments for MI/RI.

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Glucose-Sensitive Polyphosphoester Diblock Copolymer for an Insulin Delivery System

Cited by 16 publications

References 68 publications

Glucose-Sensitive Core-Cross-Linked Nanoparticles Constructed with Polyphosphoester Diblock Copolymer for Controlling Insulin Delivery

Glucose-Sensitive Core-Cross-Linked Nanoparticles Constructed with Polyphosphoester Diblock Copolymer for Controlling Insulin Delivery

Insulin Delivery Using Dynamic Covalent Boronic Acid/Ester‐Controlled Release

Nanoparticles capable of managing hypoglycemia and preventing myocardial ischemia‐reperfusion injury

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