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

Li, Yuqiang; Zhang, Yunyan; Yang, Junjiao; Yang, Jing

doi:10.1039/c7ra00418d

Cited by 4 publications

(7 citation statements)

References 62 publications

(39 reference statements)

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“…Polymers. As reported, 47,49 the amphiphilic polymers, MPEG- S2). In the presence of HBr/HOAc, the benzyl protection groups were successfully removed from the PBLG blocks of P-4 (Scheme 1).…”

Section: Synthesis and Characterization Of Amphiphilicsupporting

confidence: 51%

“…As reported, , the amphiphilic polymers, MPEG- b -PPBDEMA (P-1) and MPEG- b -PBLG (P-4) (Scheme ), were prepared by atom transfer radical polymerization (ATRP) and ring-opening polymerization (ROP) with MPEG-Br and MPEG-NH 2 as the macroinitiators, respectively. From the 1 H NMR results shown in Figure S1, the degree of polymerization (DP) of the PPBDEMA block in P-1 was calculated to be 75 by comparing the peak areas for the phenyl ring (δ = 7.78 ppm) of the PPBDEMA segment to that for the methyl group (δ = 3.43 ppm) of the MPEG block.…”

Section: Resultsmentioning

confidence: 99%

“…43−46 The coassembly of amphiphilic copolymers is one highly efficient and convenient method to obtain nanoparticles with the special properties of the individual copolymers. 47 Inspired by the higher ordered structures of synthetic polypeptides, we are curious whether simple changes in the secondary conformation of the nanocarriers via the coassembly of PBA-based polymers and amphiphilic polymers with polypeptide blocks will generate a great impact on the self-regulated response of the overall materials.…”

Section: Introductionmentioning

confidence: 99%

“…Diabetes is a chronic disease where the body is unable to regulate blood glucose level within the normal range. , Traditional administrations of exogenous insulin via subcutaneous injection and noninvasive therapy such as oral, nasal, transdermal, and ocular delivery systems cannot regulate insulin release continuously and automatically in response to the blood glucose fluctuation because the glucose-sensing and insulin-releasing modules are not directly integrated. , To resolve these issues for diabetic patients and reduce the incidence of hyperglycemia and hypoglycemia, smart therapies called closed-loop insulin release, which can precisely control the insulin amount on demand, have been broadly developed. − Among them, phenylboronic acid (PBA)-based glucose-triggered systems have attracted great interest because PBA and its derivatives can conjugate with glucose molecules to form a reversible ester bond for the achievement of the closed-loop effect. , Until now, a variety of PBA-based glucose-responsive materials, especially in the form of nanoparticles including nanogels (microgels), , micelles, − vesicles, − and nanocapsules, , have been broadly explored to improve their glucose concentration sensitivity and on–off regulated response in a physiological environment. Most of the PBA-based nanocarriers in the reported examples rely on the versatile architectural design of the glucose-responsive materials themselves to modulate the sensitivity of insulin release in response to blood glucose level changes. − The coassembly of amphiphilic copolymers is one highly efficient and convenient method to obtain nanoparticles with the special properties of the individual copolymers . Inspired by the higher ordered structures of synthetic polypeptides, we are curious whether simple changes in the secondary conformation of the nanocarriers via the coassembly of PBA-based polymers and amphiphilic polymers with polypeptide blocks will generate a great impact on the self-regulated response of the overall materials.…”

Section: Introductionmentioning

confidence: 99%

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Impact of Secondary Structure of Polypeptides on Glucose Concentration Sensitivity of Nanocarriers for Insulin Delivery

Yang

et al. 2018

ACS Appl. Bio Mater.

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A reasonably intelligent response to glucose concentration fluctuations is crucial for developing a self-regulated insulin delivery system. Inspired by the relationship between the higher ordered structures of proteins and their versatile functions, the introduction of polypeptides capable of mimicking different secondary structures into the delivery system will be anticipated for adjusting glucose concentration sensitivity. Herein, this work presents the impact of different secondary structural architectures of polypeptide blocks on the stability of glucose-responsive complex nanoparticles (CNPs) in the normal physiological environment and their response to the stimuli of normoglycemic and hyperglycemic conditions in vitro. Results from the conformational investigations of the CNPs carried out using circular dichroism and insulin release under the different stimuli suggested that the stability and glucose sensitivity of the CNPs are closely related to the secondary structure composition of the polypeptide blocks. The CNPs with a dominant α-helix structure exhibit a promising potential to improve normal glycemic control and to reduce the incidences of hyperglycemia and hypoglycemia both in vitro and in vivo.

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Section: Synthesis and Characterization Of Amphiphilicsupporting

confidence: 51%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Impact of Secondary Structure of Polypeptides on Glucose Concentration Sensitivity of Nanocarriers for Insulin Delivery

Yang

et al. 2018

ACS Appl. Bio Mater.

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“…Comparatively, PBA and its derivatives have been broadly studied as candidate materials for sensors and drug delivery systems for sugar‐regulated human diseases due to their versatility for different designs and better stability . Indeed, a variety of PBA‐based glucose‐responsive materials especially in the form of nanoparticles including micelles, vesicles and mesoporous silica nanoparticles have exhibited effective glucose sensitivity at physiological pH …”

Section: Introductionmentioning

confidence: 99%

Thermo‐ and glucose‐sensitive microgels with improved salt tolerance for controlled insulin release in a physiological environment

Yang

et al. 2018

Polymer International

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The response to temperature and glucose, high salt tolerance and self-regulated drug delivery are simultaneously probable by applying a multifunctional microgel in a rational design by a colloid chemistry method. Such smart microgels were fabricated with thermoresponsive N-isopropylacrylamide, glucose-sensitive (2-phenylboronic esters-1,3-dioxane-5-ethyl)methyl acrylate (PBDEMA) and water-soluble crosslinker poly(ethylene glycol) diacrylate through a precipitation emulsion method. These colloidal nanoparticles exhibited PBDEMA-composition-dependent responsive behavior with changing temperature and ionic strength. Amongst them, the microgel with 20.7 mol% PBDEMA with a narrow size distribution is suitable for diabetes treatment because it can adapt to the surrounding medium of different glucose concentrations over a clinically relevant range (0-2.0 mg mL −1 ), control the release of preloaded insulin and is highly stable under normal physiological conditions. Preliminary experiments suggest these highly stable microgels have the potential to be used for self-regulated therapy and monitoring the response to treatment.

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

Abstract: A facile strategy toward improving the salt-tolerance of a glucose-responsive delivery system to realize self-

Cited by 4 publications

References 62 publications

Impact of Secondary Structure of Polypeptides on Glucose Concentration Sensitivity of Nanocarriers for Insulin Delivery

Impact of Secondary Structure of Polypeptides on Glucose Concentration Sensitivity of Nanocarriers for Insulin Delivery

Thermo‐ and glucose‐sensitive microgels with improved salt tolerance for controlled insulin release in a physiological environment

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

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