title: Pharmacodynamics and toxicity of vasoactive intestinal peptide for intranasal administration.
abstract: The aim of this work was to study the nasal route for the delivery of vasoactive intestinal peptide (VIP) to the brain and to evaluate the toxicity of VIP nasal spray. Mice were injected intracerebroventricularly with the aggregated Abeta25-35 to mimic Alzheimer's disease. Following administration, different groups of mice were treated over one week, and their spatial learning and memory capacities were evaluated by the Morris water maze test. The toxicity of VIP nasal spray was evaluated by examining the morphology of individual rat nasal mucosa cilia and the pathology of rat nasal mucosa. Rats receiving intranasal VIP (40 microg/ml) showed good spatial memory relative to the Abeta25-35 model group, but the escape latency did not show any statistically significant difference. Intranasal administration of VIP nasal spray (200 microg/ml) improved deficits in spatial memory to the point that test animals receiving intranasal VIP showed no statistically significant differences from the normal control group in escape latency. This indicated that the nasal spray method could increase the quantity of VIP entering the brain and protect the central nervous systems of mice. Toxicity evaluation showed that the preparation could cause minor irritation, which resolved spontaneously within a week at the end of treatment. In conclusion, VIP can be delivered successfully to the brain using the intranasal route.
authors: College of Pharmaceutical Science, Hebei Medical University, Beijing, China. cuixu5693255@163.com
authors: Xu
authors: X
authors: Cui
authors: De-Ying
authors: DY
authors: Cao
authors: Zhi-Min
authors: ZM
authors: Wang
authors: Ai-Ping
authors: AP
authors: Zheng
mesh_terms: D000281:Administration, Intranasal; D000336:Aerosols; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D002923:Cilia / Q000187:drug effects / Q000648:ultrastructure; D007276:Injections, Intraventricular; D007509:Irritants; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000523:psychology; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009297:Nasal Mucosa / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D010446:Peptide Fragments / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity*
chemical_list: D000336:Aerosols; D016229:Amyloid beta-Peptides; D007509:Irritants; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D014660:Vasoactive Intestinal Peptide