神经毒素-I纳米粒鼻腔给药的脑内递送研究  

Brain delivery of neurotoxin-I-loaded nanoparticles through intranasal administration

作　　者：程巧鸳[1] 冯健[1] 李范珠[1] 

机构地区：[1]浙江中医药大学药学院,浙江杭州310053

出　　处：《药学学报》2008年第4期431-434,共4页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30371781).

摘　　要：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.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 mierodialysis 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 [/v, （95 ±10） min] or NT-Ⅰ E/v, （ 145 ± 10） min ]. The concentration to peak level （Cmax） and the area under the curves from zero to 4 h （AUC0-4h） 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.

关 键 词：神经毒素-Ⅰ 脑内递送 纳米粒 鼻腔给药 微透析技术 

分 类 号：R943[医药卫生—药剂学]