| Objective: With increasing of the population of the aged person, many brain diseases have become a serious effect to the quality of aged persons' life and it has brought great pressure and burden to social and family. Alzheimer's disease is a very important pathology type of senile dementia and according to statistics,there are more than 20 million patients suffering from AD. 98 percent of the drug delivery into the brain is made difficult by the presence of the blood-brain barrier (BBB), which is the natural physical barriers of brain. In anatomy, there is a direct link between nasal and brain, after intranasal administration some of the drugs can be absorbed by the nasal mucosa into the olfactory bulb or cerebrospinal fluid and drugs can bypass the BBB to the brain.By that way drugs can cure diseases of central nervous system. Therefore, intranasal administration is a non-invasive way to improve the brain deliver of drug, it is safe, effective and convenient. Vasoactive intestinal peptide (VIP) which is a neuropeptide composed of 28 amino acids has a significant effect in promoting memory and intelligence. Combining of the physico-chemical property VIP and the characteristics of nasal administration,we prepare a nasal drug delivery system with easy using, good patient compliance, taking action quickly and little ciliotoxicity, providing evidence for the clinical applications.Methods: The stability of VIP in different pH values, ionic strength, temperature , artificial gastric fluid and artificial intestinal fluid were investigated, and the concentration of VIP was calculated by HPLC method. To provide the theory basis for the formulation development of VIP, the chemical and biological stability of VIP were studied. The effects of VIP,ifferent kinds of chitosan,absorption enhancers and preservatives on mucociliary movement were examined using the toad palate model.we examined the effect of different VIP nasal spray with various absorption enhancers on toad palate ciliary movement in situ.Rat in situ nasal perfusion methods was used as an experimental model to investigate the effect of different concentration of chitosan and absorption enhancers on the regulation of nasal absorption of VIP. Mice were intracerebroventricular injected with the aggregated Aβ25-35 to mimic AD. The spatial learning and memory capacities of mice were measured by the Morris water maze procedure via different dmstrations of VIP. To provide the basis for the application of the preparation,the toxicity of VIP nasal spray was evaluated in irritation of Rabbit eyes,morphology of rat nasal mucosa cilium and pathology of rat nasal mucosa。Results: The results showed that The stability of VIP was pH-dependent. VIP was stable in acid and neutral solution, and almost didn't degrade during pH≤7 solution. However, it was instability in basic solution and degraded completely at 30min in pH13 solution. Ionic strength did not affect its stability. VIP was stable in freezing conditions but it degraded at low concentration in cold storage. Furthermore, VIP was degraded so quickly in artificial gastric fluid and artificial intestinal fluid that it was not suitable for oral administration.The effect of VIP and some excipients on mucociliary movement were examined. VIP show no toxicity to the ciliary movement.The order of ciliotoxicity of absorption enhancers was EDTA(0.1%) |
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