RESTRICTED DIFFUSION AND STABILITY OF CARBACHOL-FLUORESCENT NANOSPHERES INVIVO

MAPPING neuronal populations that induce behavioral state changes after pharmacological activation requires discrete localization of drug injection sites, and is limited by widespread diffusion of molecular drugs. Nanospheres with diameters of 50-100 nm can reduce diffusion significantly because of their relatively large sizes. The cholinergic agonist carbachol was radiolabeled with methyl-C-14 and incorporated within a latex nanosphere delivery system (LNDS). We quantitatively compared diffusion of C-14-carbachol within these nanospheres with that of free C-14-carbachol, demonstrating approximately ten-fold reduced radial diffusion by nanospheres 10 min to 24 h post-injection; approximately 90% of injected radioactivity was restricted to regions within approximately 100-150-mu-m and 1400-1500-mu-m respectively. Thus, incorporation of active agents such as drugs within nanospheres dramatically increases the precision of their delivery in-vivo (here about 1000-fold by volume).