Characterization of glucose-sensitive insulin release systems in simulated in vivo conditions

Traitel, Tamar; Cohen, Yachin; Kost, Joseph

doi:10.1016/s0142-9612(00)00050-8

Cited by 227 publications

(145 citation statements)

References 21 publications

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“…112 Zhao et al 113 reported the synthesis of a glucose-responsive MSN-based double delivery system for both insulin and cyclic AMP with precise control over the sequence of release. As depicted in Figure 9, gluconic acid-modified insulin (G-Ins)8 proteins were immobilized on the exterior surface of boronic acid-functionalized MSN through reversible covalent bonding between phenyl boronic acid and vicinal diols of FITC-G-Ins, giving rise to the desired FITC-G-Ins-MSN material and also serving as caps to encapsulate cyclic AMP molecules inside the mesopores of MSN.…”

Section: Glucose-responsive Drug Deliverymentioning

confidence: 99%

Mesoporous silica nanoparticles for stimuli-responsive controlled drug delivery: advances, challenges, and outlook

Song

et al. 2016

IJN

203

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Section: Glucose-responsive Drug Deliverymentioning

confidence: 99%

Mesoporous silica nanoparticles for stimuli-responsive controlled drug delivery: advances, challenges, and outlook

Song

et al. 2016

IJN

203

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“…In recent years, there has been considerable work performed in the development of cross-linked polymeric networks which are sensitive to their surrounding physiological environment and therefore would be desirable systems for site-specific drug delivery [1][2][3][4][5][6]. Possible applications of these copolymers are intranasal, intraocular, buccal, enteric and colonic delivery.…”

Section: Introductionmentioning

confidence: 99%

Elucidation of the mechanism of incorporation of insulin in controlled release systems based on complexation polymers

Morishita

Lowman

Takayama

et al. 2002

Journal of Controlled Release

151

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The objective of this study was to investigate the insulin incorporation and release properties of poly(methacrylic acid-g-ethylene glycol) P(MAA-g-EG) microparticles as a function of copolymer composition. These microparticles exhibited unique pH-responsive characteristics in which interpolymer complexes were formed in acidic media and dissociated in neutral / basic environments. The microparticles containing equimolar amounts of MAA and PEG were capable of efficient insulin loading using equilibrium partitioning (>90%). Additionally, insulin release from the gel was significantly retarded in acidic media while rapid release occurred under neutral / basic conditions. In contrast, as the amount of MAA of the polymer was increased, the entrapment efficiency of insulin within the gel greatly reduced and the insulin was readily released from the polymer network in the acidic and neutral / basic media. In addition, in order to evaluate the potential application of the microparticles to other drugs, theophylline, vancomycin, fluoresceinisothiocyanate-labeled dextrans (FITC-Ds) with average molecular weights of 4400 (FITC-D-4), 12,000 (FITC-D-10) and 19,500 were utilized as model hydrophilic drugs. The incorporation profiles showed that the uptake of theophylline and vancomycin to the microparticles was lower than that of insulin. Additionally, polymer microparticles loaded with theophylline and vancomycin exhibited pH-sensitive release behavior, however, the oscillatory behavior is less pronounced than those of insulin. The values of drug incorporation ratio showed that the microparticles were capable of incorporating almost 90% of insulin and 15% of vancomycin from solution. On the other hand, the other hydrophilic drugs showed very low incorporation efficiency to the microparticles. These data suggest that gels containing equimolar amounts of MAA:EG have the potential to be used as an oral carrier of peptide drugs, especially for insulin.

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“…This provocative discovery and concept has since been expanded by exploring the combination of insulin with diverse matrices, such as glucose-responsive gel, microparticle or nanoparticle, bioinorganic membrane, and micelle, some of which were taken into preclinical studies for in vivo proof of concept (6,7). Alternative approaches that can serve as the glucose-sensing trigger to modulate insulin release have also been attempted, such as glucose oxidase (8) and phenylboronate-based glucose sensing (9) and a GRI patch (10). Admirable progress to identify a GRI has been made (7,11), yet many obstacles remain in the creation of insulin analogs that can continuously sense and respond to blood glucose fluctuation in a minimally invasive manner.…”

Section: Introductionmentioning

confidence: 99%

A glucose-responsive insulin therapy protects animals against hypoglycemia

Yang¹,

Wu²,

Lin³

et al. 2018

JCI Insight

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Characterization of glucose-sensitive insulin release systems in simulated in vivo conditions

Cited by 227 publications

References 21 publications

Mesoporous silica nanoparticles for stimuli-responsive controlled drug delivery: advances, challenges, and outlook

Mesoporous silica nanoparticles for stimuli-responsive controlled drug delivery: advances, challenges, and outlook

Elucidation of the mechanism of incorporation of insulin in controlled release systems based on complexation polymers

A glucose-responsive insulin therapy protects animals against hypoglycemia

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