Brain transport of neurotoxin-I with PLA nanoparticles through intranasal administration in rats: a microdialysis study.
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.
College of Pharmaceutical Science, ZheJiang Chinese Medical University, 548 Binwen Road, HangZhou, 310053, China.
Qiaoyuan
Q
Cheng
Jian
J
Feng
Jianming
J
Chen
Xuan
X
Zhu
Fanzhu
F
Li
D000281:Administration, Intranasal; D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D003039:Cobra Neurotoxin Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D017551:Microdialysis / Q000379:methods*; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003039:Cobra Neurotoxin Proteins; C080422:neurotoxin-1, Naja naja oxiana