Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Design, synthesis, & biological evaluation of nanoparticle drug delivery systems.

Authors
Faraji-AH; Vlasova-II; Konduru-NV; Feng-W; Kagan-VE; Wipf-P
Source
Toxicologist 2009 Mar; 108(1):182
NIOSHTIC No.
20035248
Abstract
The prevalence of nanotechnology in medicine has grown exponentially in recent years; moreover, intense exploration into the toxicology of nanomaterials has paralleled this growth. It is known that inorganic nanoparticles - such as those made from silica - catalyze the production of damaging free radicals. This undesirable toxicity limits the medical applications of inorganic nanoparticles. However, functionalization of the reactive nanoparticle surface may mask the potential for free radical generation. Free radical scavengers - in particular, 2,2,6,6-tetramethylpiperidine- N-oxyl (TEMPO) - may be covalently attached to nanoparticles via an acid-labile oxazoline moiety, which selectively hydrolyzes to release the antioxidant payload upon lysosomal incorporation. This new release strategy may increase the biocompatibility of inorganic nanoparticles via reduction of oxidative stress pathways. As an extension, the oxazoline release mechanism may be utilized to deliver a myriad of small molecule drugs, as it is amenable to drug attachment via peptide coupling and esterification. Silica nanoparticles were prepared and their surfaces were functionalized with the oxazoline-TEMPO antioxidant release system. In addition, the nanoparticles were conjugated to fluorescein, thus permitting to monitor subcellular localization via fluorescence microscopy. The nanoparticles were coated with phosphatidylserine to allow for efficient uptake. Macrophages (RAW264.7) were incubated with these nanoparticles; rapid and extensive uptake was seen within 0.5-1 hours. The nanoparticles concentrated in lysosomes and mitochondria, with a significant reduction in superoxide generation. In summary, the toxicity associated with inorganic nanoparticles may be mitigated by surface modification with small molecule antioxidants, thus increasing their biocompatibility and prevalence in medicine and drug delivery.
Keywords
Absorption-rates; Antioxidants; Antioxidation; Biological-effects; Biological-factors; Chemical-hypersensitivity; Chemical-reactions; Drug-interaction; Exposure-assessment; Exposure-levels; Exposure-methods; Inorganic-compounds; Molecular-biology; Medical-research; Medical-treatment; Statistical-analysis; Nanotechnology
CAS No.
7631-86-9
Publication Date
20090301
Document Type
Abstract
Funding Type
Grant
Fiscal Year
2009
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-008282
Issue of Publication
1
ISSN
1096-6080
Source Name
The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland
State
PA
Performing Organization
University of Pittsburgh at Pittsburgh
TOP