Abstract
PβAE polymers have emerged as highly promising candidates for biomedical and drug delivery applications owing to their tunable, degradable and pH sensitive properties. These polymeric systems can serve as prodrug carriers for the delivery of bioactive compounds which suffer from poor aqueous solubility, low bioavailability and are biologically unstable, such as the antioxidant, quercetin. Using acrylate functionalized quercetin, it is possible to incorporate the polyphenol into the backbone of the polymer matrix, permitting slow release of the intact molecule which is perfectly timed with the polymer degradation. While formulating these quercetin conjugated PβAE matrix into nanocarriers would allow for multiple delivery routes (oral, intravenous, inhalation etc.), well known oil-water nano-emulsion formulation methods are not amenable to the crosslinked hydrolytically sensitive nanoparticle/nanogel. In this work, a single-phase reaction-precipitation method was developed to formulate quercetin conjugated PβAE nanogels (QNG) via reaction of acrylated quercetin (4-5 acrylate groups) with a secondary diamine under dilute conditions using acetonitrile as the reaction medium, resulting in a self-stabilized suspension. The proposed approach permits the post synthesis modification of the spherical nanogels with a PEGylated coating, enhancing their aqueous stability and stealth characteristics. Nanogel size was controlled by varying feed reactant concentrations, achieving drug loadings of 25-38 wt%. Uniform release of quercetin over 45-48 h was observed upon PβAE ester hydrolysis under physiological conditions with its retained antioxidant activity over the extended times. Statement of Significance Here we present the first demonstration of using poly(beta amino ester) chemistry to form nanogels composed of a bioactive polyphenol for the control of cellular oxidative stress. Previous nanogel and nanoparticle approaches, which use a water phase, are not readily amenable to PBAE chemistry due to their hydrolytic sensitivity. Here we demonstrate a simple approach to control particle size, modify surface chemistry and achieve highly regulated controlled release of active antioxidants, which can protect cells against external oxidative stress signals. This work has importance in the area of controlling material biocompatibility through augmenting the antioxidant status of cells.
Original language | English |
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Pages (from-to) | 194-204 |
Number of pages | 11 |
Journal | Acta Biomaterialia |
Volume | 27 |
DOIs | |
State | Published - Nov 2015 |
Bibliographical note
Publisher Copyright:© 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Funding
The project described was supported by a grant from the Office of Naval Research (ONR DEPSCoR) and the National Center for Research Resources and the National Center for Advancing Translational Sciences , National Institutes of Health , through Grant UL1TR000117. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Office of Naval Research or the NIH.
Funders | Funder number |
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National Center for Advancing Translational Sciences (NCATS) | |
National Center for Research Resources | |
National Institutes of Health (NIH) | |
National Institutes of Health (NIH) | |
Office of Naval Research Naval Academy | |
National Center for Research Resources | |
National Center for Advancing Translational Sciences (NCATS) | UL1TR000117 |
Keywords
- Antioxidants
- Endothelial cells
- Nanogels
- Oxidative stress
- Poly(b-amino esters)
- Quercetin
ASJC Scopus subject areas
- Biotechnology
- Biomaterials
- Biochemistry
- Biomedical Engineering
- Molecular Biology