Targeted Delivery of Anti-inflammatory and Imaging Agents to Microglial Cells with Polymeric Nanoparticles.

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 ß (IL-1ß), 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.

Electrokinetic Manipulation of Silver and Platinum Nanoparticles and Their Stochastic Electrochemical Detection.

Electrokinetic phenomena such as dielectrophoresis and electrothermal fluid flow are used to increase the rate of mass transfer of silver and platinum nanoparticles and improve their stochastic electrochemical detection. These phenomena are induced by applying a high frequency alternating current (ac) waveform between a counter electrode and a working disk microelectrode. By recording chronoamperograms at room temperature and various ac powers, it is shown that the ac heating leads to an increase in the collision frequency of studied nanoparticles with working electrode surface by a factor of ∼101-103 as well as the increase in the magnitude of the measured faradaic response. It is suggested that the developed methodology could be used in the future to improve the detection of ultralow concentrations of various important bioanalytes.