The purpose of this paper is to encapsulate neurotoxin-I（NT-I）,a kind of analgesic peptide,into polylactic acid（PLA） nanoparticles（NPs） and to evaluate their transport into the brain after intranasal administration（in） by use of microdialysis sampling technique developed in our laboratory recently.NT-I-NPs(NT-Iradiolabeled with sodium 125I-Iodide) were prepared by a double emulsification solvent evaporation method,and were characterized in terms of surface morphology,particle size distribution,zeta potential and entrapment efficiency.Then,NT-I-NPs were administered intranasally or intravenously to rats and the radioactivities in periaqueductal gray（PAG） were monitored up to 240 min utilizing the microdialysis sampling technique.Nanoparticles prepared were spherical with homogenous size distribution.Their mean particle size and zeta potential measured were（65.3±10.8） nm and（-28.6±2.3） mV,respectively.The entrapment efficiency of NT-Iencapsulated into nanoparticles was（35.5±2.8）%.The brain transport results showed that the time to peak level(Tmax) of NT-I-NPs（in） was（（65±）10） min approximately,apparently shorter compared with NT-I-NPs [iv,（95±10） min] or NT-I [iv,（145±10） min].The concentration to peak level (Cmax) and the area under the curves from zero to 4 h(AUC0-4 h) of each group followed this order: NT-I-NPs（in）>NT-I-NPs（iv） >NT-I（iv）.With nanoparticles as carriers and administered intranasally could be a potential way for centrally active peptides to improve their brain transport.Microdialysis is quite a good technique for the study of drug delivery to the brain.
