论文部分内容阅读
目的:探索利用鼻腔嗅觉区的鼻-脑通路开发治疗阿尔茨海默病(Alzheimer disease,AD)经鼻脑靶向给药系统的可行性。方法:将150只大鼠随机分为3组,分别进行灌胃给药、静脉注射给药及鼻腔给药,剂量均为8 mg.kg-1,于不同时间点取血浆和脑组织样品后用HPLC法测定各血浆及脑组织内药物浓度,用3P87软件处理数据得药动学参数。结果:氢溴酸加兰他敏鼻腔给药吸收快;大鼠鼻腔给药脑组织AUC约为灌胃给药的3.2倍、静脉注射给药的2.2倍;而血浆AUC约为灌胃给药的0.54倍、静脉注射给药的0.21倍。结论:氢溴酸加兰他敏鼻腔给药显著增加了药物在脑内的浓度,提高了药物的脑靶向性,为AD的治疗提供一种极有发展前景的给药途径。
OBJECTIVE: To explore the feasibility of nasal-brain pathway using nasal olfactory region to develop nasal-targeted drug delivery system for the treatment of Alzheimer’s disease (AD). Methods: One hundred and fifty rats were randomly divided into three groups: gavage, intravenous injection and intranasal administration respectively at the dose of 8 mg.kg-1. Plasma and brain tissue samples were taken at different time points The drug concentration in each plasma and brain tissue was determined by HPLC, and the pharmacokinetic parameters were obtained by 3P87 software. Results: The intranasal administration of galantamine hydrobromide absorbed quickly; AUC of nasal administration in rats was about 3.2 times that of intragastric administration and 2.2 times that of intravenous administration; and the plasma AUC was about intragastric administration 0.54 times, 0.21 times that of intravenous injection. CONCLUSION: Nasal administration of galantamine hydrobromide significantly increases the concentration of the drug in the brain and improves the brain targeting of the drug, providing a promising route of administration for the treatment of AD.