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Synthesis of multi-responsive poly(NIPA-co-DMAEMA)-PBA hydrogel nanoparticles in aqueous solution for application as glucose-sensitive insulin-releasing nanoparticles

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Journal of Diabetes & Metabolic Disorders Aims and scope Submit manuscript

Abstract

Objectives

This study aimed to present an innovative method for synthesizing pH-thermo-glucose responsive poly(NIPA-co-DMAEMA)-PBA hydrogel nanoparticles via single-step aqueous free radical polymerization.

Methods

The synthesis process involved free radical polymerization in an aqueous solution, and the resulting nanoparticles were characterized for their physical and chemical properties by 1H NMR, Dynamic Light Scattering (DLS) and Scanning Electron Microscopy (SEM). Insulin-loaded poly(NIPA-co-DMAEMA)-PBA hydrogel nanoparticles were prepared and evaluated for their insulin capture and release properties at different pH and temperature, in addition to different glucose concentrations, with the release profile of insulin quantitatively evaluated using the Bradford method.

Results

1H NMR results confirmed successful PBA incorporation, and DLS outcomes consistently indicated a transition to a more hydrophobic state above the Lower Critical Solution Temperature (LCST) of NIPA and DMAEMA. While pH responsiveness exhibited variation, insulin release generally increased with rising pH from acidic to neutral conditions, aligning with the anticipated augmentation of anionic PBA moieties and increased hydrogel hydrophilicity. Increased insulin release in the presence of glucose, particularly for formulations with the lowest mol % PBA, along with a slight increase for the highest mol % PBA formulation when increasing glucose from 1 to 4 mg/mL, supported the potential of this approach for nanoparticle synthesis tailored for glucose-responsive insulin release.

Conclusions

This work successfully demonstrates a novel method for synthesizing responsive hydrogel nanoparticles and underscores their potential for controlled insulin release in response to glucose concentrations. The observed pH-dependent insulin release patterns and the influence of PBA content on responsiveness highlight the versatility and promise of this nanoparticle synthesis approach for applications in glucose-responsive drug delivery systems.

Graphical abstract

Poly(NIPA) nanoparticles containing PBA moieties are normally synthesized in two or more steps in the presence of organic solvents. Here we propose a new method for the synthesis of multiresponsive hydrogel poly(NIPA-co-DMAEMA)-PBA nanoparticles in aqueous medium in a single reaction to provide a fast and effective strategy for the production of glucose-responsive multi-systems in aqueous media from free radical polymerization

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Acknowledgements

The authors acknowledge the support of College of Science (COS) - George Mason University (GMU); Dr. Barney Bishop and Dr. Remi Veneziano. All the authors contributed equally to this work.

Funding

This project was funded by the College of Science (COS), George Mason University (GMU).

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, George Mason University, Manassas, VA, 20110, USA

    Liana Chafran & Amy Carfagno

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  1. Liana Chafran
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  2. Amy Carfagno
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Liana S. Chafran and Amy Carfagno. The first draft of the manuscript was written by Liana S. Chafran and all authors contributed critically to give final approval for publication.

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Correspondence to Liana Chafran.

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Chafran, L., Carfagno, A. Synthesis of multi-responsive poly(NIPA-co-DMAEMA)-PBA hydrogel nanoparticles in aqueous solution for application as glucose-sensitive insulin-releasing nanoparticles. J Diabetes Metab Disord (2024). https://doi.org/10.1007/s40200-024-01421-7

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