Journal
ZEITSCHRIFT FUR ANORGANISCHE UND ALLGEMEINE CHEMIE
Volume 640, Issue 3-4, Pages 616-623Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/zaac.201300604
Keywords
Nanoparticle drug delivery vehicle; Insulin; Mesoporous silica nanoparticles; Stimuli-responsive drug release; Nanomedicine
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Funding
- US National Science Foundation (NSF) through NSF [DMR-0968937]
- NSF [NanoEHS-1134289]
- NSF-ACIF
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Multi-stimuli responsive porous silica nanoparticles for controlled release of insulin were synthesized by tethering insulin molecules onto boronic acid-functionalized mesoporous silica nanoparticles (BA-MSNs) and then coating the BA-MSNs with the bioadhesive and pH-sensitive polymer polyacrylic acid (PAA). The insulin molecules were conjugated onto the exterior surfaces of BA-MSNs via gluconic acid linker groups [or by making first the gluconic acid-modified insulin (Gins)]. The surfaces of the resulting BA-MSNs containing Gins were coated with PAA, which was used to protect the entrapped insulin from undergoing possible enzymatic degradations in such locations as the gastrointestinal (GI) tract. The PAA, which has excellent dispersibility and adherence to the mucosa, might also allow the permeation of such nanoparticles through the colon, and thereby improve their potential application for insulin delivery. The drug release properties of the resulting nanoparticles, denoted PAA-Gins-BA-MSNs, as well as their control samples were studied in enzyme-free simulated gastric fluid (SGF) (pH = 2.0), simulated intestinal fluid (SIF) (pH = 6.8), and phosphate buffer saline (PBS) (pH = 7.4). Because of their shrinkage at low pH and swelling at high pH, the PAA-coated MSNs exhibited pH-dependent insulin release properties. Besides pH, glucose was shown to trigger the release of insulin from the nanoparticles, which demonstrates the nanoparticles' multi-stimuli-responsive properties for controlled release of insulin. Finally, we show that the PAA-coated MSNs were non-cytotoxic.
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