This application is in response to the RFA-ES-06-008: Manufactured nanomaterials: Physicochemical principles of biocompatibility and toxicity. Recent advances in nanotechnology have enabled fabrication of novel nanoconstructs with potential commercial and biomedical applications. Some promising nanoconstructs include dendrimers and silica nanoparticles. These nanoconstructs can be fabricated with discrete, well-defined monodisperse size, shape and surface properties. However little is known about the interactions of these particles with mammalian systems including their potential to cause toxicity. The focus of this application is on systematically evaluating the influence of size, geometry, porosity and surface functionality of dendritic as well as silica nanoparticles on their toxicity and cellular uptake.
Three Specific Aims are proposed: 1. Preparation and characterization of dendrimers, porous silica nanoparticles, and silica nanotubes with discrete variations in size, charge and surface chemistry to regulate biocompatibility. 2. In vitro evaluation of toxicity, biocompatibility and mechanisms of uptake of the prepared nanomaterials as a function of physicochemical properties. 3. In vivo evaluation of biodistribution and pharmacokinetics of the nanomaterials and their subsequent correlation with physicochemical properties, toxicity and biocompatibility.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE019050-05
Application #
7916398
Study Section
Special Emphasis Panel (ZES1-SET-G (NT))
Program Officer
Drummond, James
Project Start
2007-09-28
Project End
2012-08-31
Budget Start
2010-09-01
Budget End
2012-08-31
Support Year
5
Fiscal Year
2010
Total Cost
$268,540
Indirect Cost
Name
University of Utah
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Hadipour Moghaddam, Seyyed Pouya; Yazdimamaghani, Mostafa; Ghandehari, Hamidreza (2018) Glutathione-sensitive hollow mesoporous silica nanoparticles for controlled drug delivery. J Control Release 282:62-75
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Thiagarajan, Giridhar; Sadekar, Shraddha; Greish, Khaled et al. (2013) Evidence of oral translocation of anionic G6.5 dendrimers in mice. Mol Pharm 10:988-98
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Sadekar, S; Ghandehari, H (2012) Transepithelial transport and toxicity of PAMAM dendrimers: implications for oral drug delivery. Adv Drug Deliv Rev 64:571-88
Greish, Khaled; Thiagarajan, Giridhar; Ghandehari, Hamidreza (2012) In vivo methods of nanotoxicology. Methods Mol Biol 926:235-53

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