Journal
BIOMATERIALS
Volume 30, Issue 29, Pages 5720-5728Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2009.07.004
Keywords
Nanodiamond; Insulin; Drug delivery; Wound healing; Nanomedicine
Funding
- National Science Foundation CAREER Award [CMMI-0846323]
- National Science Foundation Mechanics of Materials program [CMMI-0856492]
- V Foundation for Cancer Research V Scholars Award
- National Science Foundation Center for Scalable and Integrated NanoManufacturing (SINAM) [DMI-0327077]
- Wallace H. Coulter Foundation Early Career Award in Translational Research
- National Science Foundation National Center for Learning & Teaching in Nanoscale Science and Engineering (NCLT)
- National Institutes of Health [U54 A1065359]
- Northwestern University Ryan Fellowship
- Div Of Civil, Mechanical, & Manufact Inn
- Directorate For Engineering [0856492, 0751621] Funding Source: National Science Foundation
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Enhanced specificity in drug delivery aims to improve upon systemic elution methods by locally concentrating therapeutic agents and reducing negative side effects. Due to their robust physical properties, biocompatibility and drug loading capabilities, nanodiamonds serve as drug delivery platforms that can be applied towards the elution of a broad range of therapeutically-active compounds. In this work, bovine insulin was non-covalently bound to detonated nanodiamonds via physical adsorption in an aqueous solution and demonstrated pH-dependent desorption in alkaline environments of sodium hydroxide. Insulin adsorption to NDs was confirmed by FT-IR spectroscopy and zeta potential measurements, while both adsorption and desorption were visualized with TEM imaging, quantified using protein detection assays and protein function demonstrated by MTT and RT-PCR. NDs combined with insulin at a 4:1 ratio showed 79.8 +/- 4.3% adsorption and 31.3 +/- 1.6% desorption in pH-neutral and alkaline solutions, respectively. Additionally, a 5-day desorption assay in NaOH (pH 10.5) and neutral solution resulted in 45.8 +/- 3.8% and 2.2 +/- 1.2% desorption, respectively. MTT viability assays and quantitative RT-PCR (expression of Ins1 and Csf3/G-csf genes) reveal bound insulin remains inactive until alkaline-mediated desorption. For applications in sustained drug delivery and therapy we have developed a therapeutic protein-ND complex with demonstrated tunable release and preserved activity. (C) 2009 Elsevier Ltd. All rights reserved.
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