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In vivo Imaging and Biodistribution of Multimodal Polymeric Nanoparticles Delivered to the Optic Nerve
Author(s) -
Harrison James,
Bartlett Carole A.,
Cowin Gary,
Nicholls Philip K.,
Evans Cameron W.,
Clemons Tristan D.,
Zdyrko Bogdan,
Luzinov Igor A.,
Harvey Alan R.,
Iyer K. Swaminathan,
Dunlop Sarah A.,
Fitzgerald Melinda
Publication year - 2012
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201102648
Subject(s) - biodistribution , in vivo , mri contrast agent , optic nerve , magnetic resonance imaging , optic tract , pathology , materials science , fluorescence lifetime imaging microscopy , nanoparticle , biomedical engineering , biophysics , pharmacology , medicine , nanotechnology , anatomy , fluorescence , biology , microbiology and biotechnology , radiology , physics , quantum mechanics
The use of nanoparticles for targeted delivery of therapeutic agents to sites of injury or disease in the central nervous system (CNS) holds great promise. However, the biodistribution of nanoparticles following in vivo administration is often unknown, and concerns have been raised regarding potential toxicity. Using poly(glycidyl methacrylate) (PGMA) nanoparticles coated with polyethylenimine (PEI) and containing superparamagnetic iron oxide nanoparticles as a magnetic resonance imaging (MRI) contrast agent and rhodamine B as a fluorophore, whole animal MRI and fluorescence analyses are used to demonstrate that these nanoparticles (NP) remain close to the site of injection into a partial injury of the optic nerve, a CNS white matter tract. In addition, some of these NP enter axons and are transported to parent neuronal somata. NP also remain in the eye following intravitreal injection, a non‐injury model. Considerable infiltration of activated microglia/macrophages occurs in both models. Using magnetic concentration and fluorescence visualization of tissue homogenates, no dissemination of the NP into peripheral tissues is observed. Histopathological analysis reveals no toxicity in organs other than at the injection sites. Multifunctional nanoparticles may be a useful mechanism to deliver therapeutic agents to the injury site and somata of injured CNS neurons and thus may be of therapeutic value following brain or spinal cord trauma.