Insulin smart drug delivery nanoparticles of aminophenylboronic acid–POSS molecule at neutral pH

Abstract Self-regulated “smart” insulin administration system that mimic pancreatic endocrine function would be highly desirable for diabetes management. Here, a glucose-responsive continuous insulin delivery system is developed, where novel polyhedral oligosilsesquioxane (POSS) modified with 3‐amin...

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Autores principales:	Won Jung Kim, Yong Jin Kwon, Chung-Hyun Cho, Sang-Kyu Ye, Kyu Oh Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fc17b66df99b45fa8171c155d52bbad5
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spelling	oai:doaj.org-article:fc17b66df99b45fa8171c155d52bbad52021-11-14T12:19:40ZInsulin smart drug delivery nanoparticles of aminophenylboronic acid–POSS molecule at neutral pH10.1038/s41598-021-01216-32045-2322https://doaj.org/article/fc17b66df99b45fa8171c155d52bbad52021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01216-3https://doaj.org/toc/2045-2322Abstract Self-regulated “smart” insulin administration system that mimic pancreatic endocrine function would be highly desirable for diabetes management. Here, a glucose-responsive continuous insulin delivery system is developed, where novel polyhedral oligosilsesquioxane (POSS) modified with 3‐aminophenylboronic acid (APBA) were used to encapsulate insulin (insulin entrapment efficiency: 73.2%) to prepare a fast response, high stability, good distribution, and excellent biocompatible system. Due to the strong hydrophobicity of POSS, the POSS moiety is located at the core in aqueous solution and combines with the boronic group of APBA and the diol generated in PEG-insulin to form a nanomicelle structure, that is, nanoparticles naturally. Micelles self‐assembled from these molecules possess glucose‐responsiveness at varying glucose concentrations. The interaction of the PBA and diol containing insulin via boronate ester bond and its interchange with glucose was investigated by FT-IR, 1H NMR and XPS. Furthermore, the successful glucose-triggered release of insulin from the POSS-APBA micelles was investigated at neutral pH. A linear graph was plotted with the measured released insulin vs glucose concentrations, with a linear correlation coefficient (R2) value close to 1. Circular dichroism (CD) spectroscopy analysis was performed to measure insulin activity by comparing secondary structures of insulin, PEG-Insulin, and POSS-APBA@insulin. When confirming intracellular apoptosis signaling, cleaved caspase 3 and caspase 9 were not increased by 640 μg/ml POSS-APBA and POSS-APBA@insulin in HeLa, HDF and HUVE cells. Application in the biomedical field for controlled delivery of insulin appear to be promising.Won Jung KimYong Jin KwonChung-Hyun ChoSang-Kyu YeKyu Oh KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Won Jung Kim Yong Jin Kwon Chung-Hyun Cho Sang-Kyu Ye Kyu Oh Kim Insulin smart drug delivery nanoparticles of aminophenylboronic acid–POSS molecule at neutral pH
description	Abstract Self-regulated “smart” insulin administration system that mimic pancreatic endocrine function would be highly desirable for diabetes management. Here, a glucose-responsive continuous insulin delivery system is developed, where novel polyhedral oligosilsesquioxane (POSS) modified with 3‐aminophenylboronic acid (APBA) were used to encapsulate insulin (insulin entrapment efficiency: 73.2%) to prepare a fast response, high stability, good distribution, and excellent biocompatible system. Due to the strong hydrophobicity of POSS, the POSS moiety is located at the core in aqueous solution and combines with the boronic group of APBA and the diol generated in PEG-insulin to form a nanomicelle structure, that is, nanoparticles naturally. Micelles self‐assembled from these molecules possess glucose‐responsiveness at varying glucose concentrations. The interaction of the PBA and diol containing insulin via boronate ester bond and its interchange with glucose was investigated by FT-IR, 1H NMR and XPS. Furthermore, the successful glucose-triggered release of insulin from the POSS-APBA micelles was investigated at neutral pH. A linear graph was plotted with the measured released insulin vs glucose concentrations, with a linear correlation coefficient (R2) value close to 1. Circular dichroism (CD) spectroscopy analysis was performed to measure insulin activity by comparing secondary structures of insulin, PEG-Insulin, and POSS-APBA@insulin. When confirming intracellular apoptosis signaling, cleaved caspase 3 and caspase 9 were not increased by 640 μg/ml POSS-APBA and POSS-APBA@insulin in HeLa, HDF and HUVE cells. Application in the biomedical field for controlled delivery of insulin appear to be promising.
format	article
author	Won Jung Kim Yong Jin Kwon Chung-Hyun Cho Sang-Kyu Ye Kyu Oh Kim
author_facet	Won Jung Kim Yong Jin Kwon Chung-Hyun Cho Sang-Kyu Ye Kyu Oh Kim
author_sort	Won Jung Kim
title	Insulin smart drug delivery nanoparticles of aminophenylboronic acid–POSS molecule at neutral pH
title_short	Insulin smart drug delivery nanoparticles of aminophenylboronic acid–POSS molecule at neutral pH
title_full	Insulin smart drug delivery nanoparticles of aminophenylboronic acid–POSS molecule at neutral pH
title_fullStr	Insulin smart drug delivery nanoparticles of aminophenylboronic acid–POSS molecule at neutral pH
title_full_unstemmed	Insulin smart drug delivery nanoparticles of aminophenylboronic acid–POSS molecule at neutral pH
title_sort	insulin smart drug delivery nanoparticles of aminophenylboronic acid–poss molecule at neutral ph
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fc17b66df99b45fa8171c155d52bbad5
work_keys_str_mv	AT wonjungkim insulinsmartdrugdeliverynanoparticlesofaminophenylboronicacidpossmoleculeatneutralph AT yongjinkwon insulinsmartdrugdeliverynanoparticlesofaminophenylboronicacidpossmoleculeatneutralph AT chunghyuncho insulinsmartdrugdeliverynanoparticlesofaminophenylboronicacidpossmoleculeatneutralph AT sangkyuye insulinsmartdrugdeliverynanoparticlesofaminophenylboronicacidpossmoleculeatneutralph AT kyuohkim insulinsmartdrugdeliverynanoparticlesofaminophenylboronicacidpossmoleculeatneutralph
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Insulin smart drug delivery nanoparticles of aminophenylboronic acid–POSS molecule at neutral pH

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