Targeted Delivery of Anti-inflammatory and Imaging Agents to Microglial Cells with Polymeric Nanoparticles
Autor: | Jason Bonezzi, Leah P. Shriver, Robert Clements, Yang H. Yun, John Shelestak, Aliaksei Boika, Celina Cahalane |
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Rok vydání: | 2020 |
Předmět: |
Polymers
Anti-Inflammatory Agents Fluorescent Antibody Technique Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy Cell Line Proinflammatory cytokine Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Discovery medicine Animals Metabolomics Macrophage Neuroinflammation Rolipram Microscopy Confocal Innate immune system Microglia 021001 nanoscience & nanotechnology Magnetic Resonance Imaging Organophosphates PLGA medicine.anatomical_structure chemistry Drug delivery Cancer research Nanoparticles Molecular Medicine 0210 nano-technology medicine.drug |
Zdroj: | Molecular Pharmaceutics. 17:1816-1826 |
ISSN: | 1543-8392 1543-8384 |
DOI: | 10.1021/acs.molpharmaceut.9b00489 |
Popis: | Insult to the central nervous system (CNS) results in an early inflammatory response, which can be exploited as an initial indicator of neurological dysfunction. Nanoparticle drug delivery systems provide a mechanism to increase the uptake of drugs into specific cell types in the CNS such as microglia, the resident macrophage responsible for innate immune response. In this study, we developed two nanoparticle-based carriers as potential theranostic systems for drug delivery to microglial cells. Poly(lactic-co-glycolic) acid (PLGA)- and l-tyrosine polyphosphate (LTP)-based nanoparticles were synthesized to encapsulate the magnetic resonance imaging (MRI) contrast agent, gadolinium-diethylenetriaminepentaacetic acid (Gd[DTPA]), or the anti-inflammatory drug, rolipram. Robust uptake of both polymer formulations by microglial cells was observed with no evidence of toxicity. In mixed glial cultures, we observed a preferential internalization of nanoparticles by microglia compared to that of astrocytes. Moreover, exposure of our nanoparticles to microglial cells did not induce the release of the proinflammatory cytokines, tumor necrosis factor α (TNF-α), interleukin-1 β (IL-1β), or interleukin-6 (IL-6). These studies provide a foundation for the development of LTP nanoparticles as a platform for the delivery of imaging agents and drugs to the sites of neuroinflammation. |
Databáze: | OpenAIRE |
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