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Supplementation of Polymeric Reservoirs with Redox-Responsive Metallic Nanoparticles as a New Concept for the Smart Delivery of Insulin in Diabetes

Type 1 diabetes is caused by the inability of the pancreatic beta cells to produce sufficient amounts of insulin, an anabolic hormone promoting the absorption of the blood glucose by various cells in the body, primarily hepatocytes and skeletal muscle cells. This form of impaired metabolism has been...

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Autor principal: Uskoković, Vuk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9862131/
https://www.ncbi.nlm.nih.gov/pubmed/36676521
http://dx.doi.org/10.3390/ma16020786
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author Uskoković, Vuk
author_facet Uskoković, Vuk
author_sort Uskoković, Vuk
collection PubMed
description Type 1 diabetes is caused by the inability of the pancreatic beta cells to produce sufficient amounts of insulin, an anabolic hormone promoting the absorption of the blood glucose by various cells in the body, primarily hepatocytes and skeletal muscle cells. This form of impaired metabolism has been traditionally treated with subcutaneous insulin injections. However, because one such method of administration does not directly correspond to the glucose concentrations in the blood and may fail to reduce hyperglycemia or cause hypoglycemia, the delivery of insulin in a glucose-dependent manner has been researched intensely in the present and past. This study tested the novel idea that the supplementation of polymeric reservoirs containing insulin with metallic nanoparticle precursors responsive to the redox effect of glucose could be used to create triggers for the release of insulin in direct response to the concentration of glucose in the tissue. For that purpose, manganese oxide nanoparticles were dispersed inside a poly(ε-caprolactone) matrix loaded with an insulin proxy and the resulting composite was exposed to different concentrations of glucose. The release of the insulin proxy occurred in direct proportion to the concentration of glucose in the medium. Mechanistically, as per the central hypothesis of the study, glucose reduced the manganese cations contained within the metal oxide phase, forming finer and more dissipative zero-valent metallic nanoparticles, thus disrupting the polymeric network, opening up pores in the matrix and facilitating the release of the captured drug. The choice of manganese for this study over other metals was justified by its use as a supplement for protection against diabetes. Numerical analysis of the release mechanism revealed an increasingly nonlinear and anomalous release accompanied by a higher diffusion rate at the expense of chain rigidity as the glucose concentration increased. Future studies should focus on rendering the glucose-controlled release (i) feasible within the physiological pH range and (ii) sensitive to physiologically relevant glucose concentrations. These technical improvements of the fundamental new concept proven here may bring it closer to a real-life application for the mitigation of symptoms of hyperglycemia in patients with diabetes.
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spelling pubmed-98621312023-01-22 Supplementation of Polymeric Reservoirs with Redox-Responsive Metallic Nanoparticles as a New Concept for the Smart Delivery of Insulin in Diabetes Uskoković, Vuk Materials (Basel) Article Type 1 diabetes is caused by the inability of the pancreatic beta cells to produce sufficient amounts of insulin, an anabolic hormone promoting the absorption of the blood glucose by various cells in the body, primarily hepatocytes and skeletal muscle cells. This form of impaired metabolism has been traditionally treated with subcutaneous insulin injections. However, because one such method of administration does not directly correspond to the glucose concentrations in the blood and may fail to reduce hyperglycemia or cause hypoglycemia, the delivery of insulin in a glucose-dependent manner has been researched intensely in the present and past. This study tested the novel idea that the supplementation of polymeric reservoirs containing insulin with metallic nanoparticle precursors responsive to the redox effect of glucose could be used to create triggers for the release of insulin in direct response to the concentration of glucose in the tissue. For that purpose, manganese oxide nanoparticles were dispersed inside a poly(ε-caprolactone) matrix loaded with an insulin proxy and the resulting composite was exposed to different concentrations of glucose. The release of the insulin proxy occurred in direct proportion to the concentration of glucose in the medium. Mechanistically, as per the central hypothesis of the study, glucose reduced the manganese cations contained within the metal oxide phase, forming finer and more dissipative zero-valent metallic nanoparticles, thus disrupting the polymeric network, opening up pores in the matrix and facilitating the release of the captured drug. The choice of manganese for this study over other metals was justified by its use as a supplement for protection against diabetes. Numerical analysis of the release mechanism revealed an increasingly nonlinear and anomalous release accompanied by a higher diffusion rate at the expense of chain rigidity as the glucose concentration increased. Future studies should focus on rendering the glucose-controlled release (i) feasible within the physiological pH range and (ii) sensitive to physiologically relevant glucose concentrations. These technical improvements of the fundamental new concept proven here may bring it closer to a real-life application for the mitigation of symptoms of hyperglycemia in patients with diabetes. MDPI 2023-01-13 /pmc/articles/PMC9862131/ /pubmed/36676521 http://dx.doi.org/10.3390/ma16020786 Text en © 2023 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Uskoković, Vuk
Supplementation of Polymeric Reservoirs with Redox-Responsive Metallic Nanoparticles as a New Concept for the Smart Delivery of Insulin in Diabetes
title Supplementation of Polymeric Reservoirs with Redox-Responsive Metallic Nanoparticles as a New Concept for the Smart Delivery of Insulin in Diabetes
title_full Supplementation of Polymeric Reservoirs with Redox-Responsive Metallic Nanoparticles as a New Concept for the Smart Delivery of Insulin in Diabetes
title_fullStr Supplementation of Polymeric Reservoirs with Redox-Responsive Metallic Nanoparticles as a New Concept for the Smart Delivery of Insulin in Diabetes
title_full_unstemmed Supplementation of Polymeric Reservoirs with Redox-Responsive Metallic Nanoparticles as a New Concept for the Smart Delivery of Insulin in Diabetes
title_short Supplementation of Polymeric Reservoirs with Redox-Responsive Metallic Nanoparticles as a New Concept for the Smart Delivery of Insulin in Diabetes
title_sort supplementation of polymeric reservoirs with redox-responsive metallic nanoparticles as a new concept for the smart delivery of insulin in diabetes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9862131/
https://www.ncbi.nlm.nih.gov/pubmed/36676521
http://dx.doi.org/10.3390/ma16020786
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