The central purpose of this research is to develop a flexible system for selective delivery of fluorescent dyes, photoactive agents and drugs to subpopulations of neurons deep within the rodent nervous system in vivo. A novel latex nanosphere delivery system (LNDS) will be developed and refined to allow neuroanatomical, developmental, and pharmacologic studies. During Phase I, the LNDS will be developed as a neuroanatomical research tool. Phase II would continue these research and development efforts while emphasizing development of selective drug delivery via the LNDS. Fluorescent dyes and photoactive agents will be incorporated within latex nanospheres of defined size, surface properties, and neuronal selectivity. Nanosphere transport within the rodent nervous system will be quantified.
Specific Aim I will be directed toward the fabrication and optimization of several types of LNDS.
Specific Aim II will focus on analysis and characterization of the nanospheres.
Specific Aims III and IV involve assessment of uptake by cultured rat neocortical neurons prior to qualitative and quantitative assessment of transport by the LNDS within two model systems: callosal projections to motor cortex and retinal ganglion cell projections to superior colliculus in rodents. Preliminary studies have demonstrated LNDS production, analyses, and biological transport. Thus, the state is set to develop this uniquely powerful methodology to produce uniform, submicron particles for selective cell targeting. The neuroscience community in particular and the biomedical community in general will benefit from a generally applicable LNDS technology. It is estimated that approximately 5,000-10,000 neuroscientists would purchase such products in the first year alone for application toward the study of development, regeneration, and transplantation within the CNS. The potential for cell specific drug delivery system is of clearly large commercial interest.
| Madison, R; Macklis, J D; Thies, C (1990) Latex nanosphere delivery system (LNDS): novel nanometer-sized carriers of fluorescent dyes and active agents selectively target neuronal subpopulations via uptake and retrograde transport. Brain Res 522:90-8 |
| Macklis, J D; Madison, R D (1990) Progressive incorporation of propidium iodide in cultured mouse neurons correlates with declining electrophysiological status: a fluorescence scale of membrane integrity. J Neurosci Methods 31:43-6 |
