鼻腔给药尼莫地平纳米乳的制备及脑组织靶向性初步评价

 目的 研制鼻腔给药尼莫地平（Nim）纳米乳制剂,并对其理化性质及脑组织靶向性作出初步评价。方法 采用滴加水法制备纳米乳,考察空白纳米乳和尼莫地平纳米乳（NimNE）的黏度、pH、粒径、粒径分布、ξ电位和电导率;用蟾蜍上颚黏膜考察尼莫地平纳米乳的黏膜刺激性;大鼠鼻腔给予尼莫地平纳米乳与尾静脉注射尼莫地平纳米乳注射液对照,用HPLC测定给药后血浆和脑组织中尼莫地平纳米乳的浓度。结果 制备的纳米乳黏度和pH均适合鼻腔给药,粒径均在20~30 nm之间,黏膜刺激性小;在240 min内,鼻腔给药的AUC_brain/AUC_plasma高于静脉给药的AUC_brain/AUC_plasma。结论 尼莫地平纳米乳给药方便,刺激性小,适宜鼻腔给药,与尼莫地平纳米乳注射液相比更具有脑组织靶向性。

Preparation of Nimodipine Nanoemulsion for Intranasal Delivery and Preliminary Studies on Its Brain Tissue Targeting

OBJECTIVE To prepare nimodipine-loaded nanoemulsion(NimNE) suitable for intranasal administration and preliminary investigate their physical and chemical properties and brain tissue targeting.METHODS Nanoemulsion were prepared using titration method and characterized for viscosity,pH,globule size and size distributions,Zeta potential and ciliotoxicity.Biodistribution of NimNE and Nim solution in the brain tissue and plasma of rats following intranasal and intravenous administrations were examined using HPLC.RESULTS The optimal nanoemulsion formulation consisted of isopropyl myristate(IPM),solutol HS-15/glycerin(4∶1) and water and were transparent and stable with mean globule size between 20 to 30 nm and almost no ciliotoxicity.After intranasal(in) administration of NimNE at a dose of 2 mg·kg-1,the ratios of AUC in brain tissues to that in plasma obtained after nasal administration were significantly higher than those after iv administration in 240 min.CONCLUSION These results suggest that the nanoemulsion system is a promising approach for intranasal delivery of Nim to brain tissue.