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.
Highlights
Diabetes which is a metabolic disease characterized by hyperglycemia, and the high blood sugar causes various symptoms and complications to detriment the quality of life
We report on the design of a polyhedral oligosilsesquioxane (POSS) based organic–inorganic hybrid smart drug delivery system which reacts sensitively to glucose in in-vivo pH conditions and releases insulin through an interchange reaction
The new peak at 1470 cm−1 in the POSS–aminophenylboronic acid (APBA) spectrum have confirmed caused by the C–N, C–N–C stretching, C–C stretching, and B–O stretching of APBA, but these peaks are absent in the spectra of POSS
Summary
Diabetes which is a metabolic disease characterized by hyperglycemia, and the high blood sugar causes various symptoms and complications to detriment the quality of life. PBA and its derivatives known to be capable of a reversible boronate group formation exhibit a high affinity towards cis-diol compounds and it is well known that a PBA functionalized moiety may be utilized as a glucose sensitive drug delivery system[16]. (3) Stable boric acid-polyol reaction are made possible under neutral pH conditions (4) The denaturalization of the protein drug is minimized by enhancement of the physicochemical stability through the loading of the protein insulin drug onto POSS. We report on the design of a POSS based organic–inorganic hybrid smart drug delivery system which reacts sensitively to glucose in in-vivo pH conditions and releases insulin through an interchange reaction. The biocompatibility was studied to explore the applicability as an innocuous hybrid nano drug delivery system
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