Brain transport of neurotoxin‐I with PLA nanoparticles through intranasal administration in rats: a microdialysis study

Abstract The purpose of this study was to encapsulate neurotoxin‐I (NT‐I) within polylactic acid (PLA) nanoparticles (NPs) and to evaluate their transport into the brain after intranasal administration (i.n.) using a microdialysis sampling technique. NT‐I‐NPs (NT‐I radiolabeled with sodium [ 125 I]iodide) were prepared and characterized. Then, NT‐I‐NPs were administered i.n. or i.v. to rats and the radioactivities in the olfactory bulbs were monitored for up to 240 min. The nanoparticles prepared were spherical with a homogenous size distribution. The mean particle size, zeta potential and entrapment efficiency were −28.6±2.3 mV, 65 nm and 35.5±2.8%, respectively. The brain transport results showed that the time to reach the peak level ( T max ) of NT‐I‐NPs (i.n . ) was 65 min, shorter than NT‐I‐NPs (i.v.) (95 min) or NT‐I (i.v . ) (145 min). The concentration at peak level ( C max ) and the total area under the concentration–time curves from zero to 4 h ( AUC 0–4 h ) of each group followed the following order: NT‐I‐NPs (i.n.)>NT‐I‐NPs (i.v . )>NT‐I (i.v . ). The corresponding absolute bioavailabilities (Fabs) of NT‐I‐NPs (i.n.) were about 160%, 196% with NT‐I‐NPs (i.v.) and NT‐I (i.v.) as reference preparations, respectively. The brain delivery of NT‐I could be enhanced with PLA nanoparticles either through i.n. or i.v. administration. Furthermore , the enhancement was more significant for i.n. than for i.v. administration. Nanoparticles as carriers would be a potential way to improve the brain transport for centrally active peptides. Copyright © 2008 John Wiley & Sons, Ltd.