In vivo Imaging and Biodistribution of Multimodal Polymeric Nanoparticles Delivered to the Optic Nerve

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 8; no. 10; pp. 1579 - 1589
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 21.05.2012; WILEY‐VCH Verlag
• Subjects: Animals; biomedical applications; Female; fluorescence; Imaging, Three-Dimensional - methods; in vivo imaging; Intravitreal Injections; Magnetic Resonance Imaging; magnetism; Microscopy, Fluorescence; nanoparticles; Nanoparticles - administration & dosage; Optic Nerve - metabolism; Optic Nerve - pathology; Polymers - administration & dosage; Rats; Retina - pathology; Time Factors; Tissue Distribution
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.201102648

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. Whole animal magnetic resonance imaging (MRI) and fluorescence analyses demonstrate that poly(glycidyl methacrylate) (PGMA) nanoparticles coated with polyethylenimine (PEI) and containing an MRI contrast agent (superparamagnetic iron oxide nanoparticles) and fluorophore (rhodamine B), remain close to the site of injection into a partial injury of the optic nerve, which is a central nervous system white matter tract.