摘要
目的:优选重组水蛭素-2(rHV2)鼻腔给药纳米粒冻干粉最佳制备工艺;考察rHV2纳米粒冻干粉稳定性及经家兔鼻黏膜的体外渗透特性。方法:选用不同冻干保护剂制备水蛭素纳米粒冻干粉末,以外观、再分散性及包封率作为评价指标,对冻干保护剂及制备工艺进行优选,并考察了光照、高温等因素对冻干粉的影响;采用直立式扩散池法,以家兔鼻中隔黏膜为渗透屏障,测定rHV2壳聚糖溶液、rHV2纳米粒溶液及冻干粉的渗透系数(P),并计算与rHV2生理盐水溶液的促渗比(ER)。结果:rHV2鼻腔给药纳米粒冻干粉最佳制备工艺为:用5%甘露醇与葡萄糖(1∶1)作为冻干保护剂,于-70℃预冻24h后,置真空冻干箱中冷冻干燥,24h后取出,该冻干粉中rHV2的含量为1.1μg/mg。光照对rHV2纳米粒冻干粉的外观、再分散性以及包封率影响均较小,而高温对rHV2纳米粒冻干粉的影响较大;rHV2壳聚糖纳米粒具有较高的渗透系数,是生理盐水组的5倍多,冻干粉仍然保持了良好的渗透性。结论:壳聚糖鼻腔给药纳米粒冻干粉有可能成为rHV2鼻腔给药的良好给药剂型。
Objective：To optimize the freeze-dried powder preparation technology of recombinate hirudin-2 （rHV2） nanoparticle which has bio-adhesive characteristic for nasal delivery, also to investigate its stability and permeability through nasal membrane in vitro. Methods： Taking the appearance, rediffusion of nanoparticle and rHV2 encapsulation efficiency as the evaluation indexes. Cryoproteetor, the preparative technique and the effect of illumination and high temperature factors on its stability for rHV2 freeze-dried powder were investigated. Using Fraze diffusion cell technique, the permeability of rHV2 across rabbit nasal mucous membrane in ehitosan solution, chitosan nanoparticle, and nanoparticle frozen-dried powder were compared with that in normal saline solution. Results：The optimized preparation of rHV2 nanoparticle freeze-dried powder was as follows：5% trehalose and glucose （1 ： 1 ） was used as cryoprotector, nanopartiele solution was freezed for 24 h in vacuum frozen-dryer after being pre-freezed for 24 h. The content of rHV2 in the freeze-dried powder was 1.1 μg/mg. Illumination had little effect on the appearance, rediffusion and encapsulation efficiency of the rHV2 freeze-dried powder. High temperature could obviously influence the appearance of nanoparticle freeze-dried powder. The permeability coefficient （P） of nanoparticle was 5 times more than that in chictonson solution. It was indicated that chitosan nanoparticle has effect on increasing the permeability of rHV2. Conclusion：The freeze-dried powder of chitosan nanoparticle can be a good nasal preparation of rHV2.
出处
《中药材》
CAS
CSCD
北大核心
2013年第6期999-1002,共4页
Journal of Chinese Medicinal Materials
基金
国家科技重大专项课题(2009ZX09502-008)
关键词
重组水蛭素-2(rHV2)
纳米粒
鼻腔给药
冻干粉
制备工艺
渗透特性
Recombinate hirudin-2 （ rHV2 ）
Bio-adhesive nanoparticle
Nasal delivery
Freeze-dried powder
Preparation technology
Permeability
