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Issue 19, 2015
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Establishment of a controlled insulin delivery system using a glucose-responsive double-layered nanogel

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Abstract

Glucose-responsive insulin delivery systems have been proposed as a promising alternative to conventional intramuscular administration methods, which causes low patient compliance due to the requirement of multiple administration. In addition, protein-based glucose-responsive systems using glucose oxidase and lectin have not achieved success in clinical trials because of their low biostability and potential cytotoxicity. In order to overcome these issues, the phenylboronic acid (PBA)-derivatives converted to hydrophilic moieties with an elevated glucose level play a key role in controlled insulin delivery systems due to their better biostability and high biocompatibility. In order to endow glucose-responsiveness to insulin delivery carriers using PBA derivatives, a glycol chitosan (GC)/sodium alginate (SA)-poly(L-glutmate-co-N-3-L-glutamylphenylboronic acid) (PGGA) graft polymer double-layered nanogel is synthesized by N-carboxyanhydride (NCA) polymerization and carbodiimide coupling reactions. The GC/SA-PGGA double-layered nanogel controllably releases insulin at diabetic glucose levels in vitro, and shows high biocompatibility, determined by cell viability and a hemolysis assay. Moreover, controlled insulin release at high glucose levels can be accomplished using the GC/SA-PGGA double-layered nanogel in mouse studies. Therefore, the GC/SA-PGGA double-layered nanogel characterized by glucose-sensitivity and superior biocompatibility may act as a potential platform for advanced insulin delivery systems.

Graphical abstract: Establishment of a controlled insulin delivery system using a glucose-responsive double-layered nanogel

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Publication details

The article was received on 18 Dec 2014, accepted on 23 Jan 2015 and first published on 23 Jan 2015


Article type: Paper
DOI: 10.1039/C4RA16656F
Citation: RSC Adv., 2015,5, 14482-14491
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    Establishment of a controlled insulin delivery system using a glucose-responsive double-layered nanogel

    D. Lee, K. Choe, Y. Jeong, J. Yoo, S. M. Lee, J. Park, P. Kim and Y. Kim, RSC Adv., 2015, 5, 14482
    DOI: 10.1039/C4RA16656F

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