葛根素-壳聚糖修饰β-环糊精鼻用超分子凝胶的制备及抗偏头痛药效评价OA

Objective To develop a puerarin-loaded supramolecular gel based on chitosan-modified β-cyclodextrin(Pur@CS-β-CD Gel),optimize its formulation,and evaluate its potential for nasal delivery and anti-migraine efficacy.Methods The Pur@CS-β-CD Gel formulation was optimized using single-factor experiments and Box-Behnken design-response surface methodology(BBD-RSM).The optimized Pur@CS-β-CD Gel was characterized for its microstructure,pH value,stability,and in vitro release profile.A chronic migraine rat model was established.The therapeutic efficacy was assessed through behavioral indicators and by measuring the levels of calcitonin gene-related peptide(CGRP),5-hydroxytryptamine(5-HT),and interleukin-1 β(IL-1β)in brain tissue.Results The optimal formulation consisted of CS-β-CD and sodium carboxymethylcellulose at a mass ratio of 1∶9,a total polymer concentration of 2.6％,and 40 mg of puerarin.The resulting Pur@CS-β-CD Gel exhibited a three-dimensional porous structure,a pH of 6.5,good stability,and a biphasic in vitro release profile characterized by an initial rapid release(82.75％within 4 h)followed by sustained release,with no obvious nasal-mucosal irritation.Pharmacodynamic studies demonstrated that Pur@CS-β-CD Gel significantly improved migraine-related behavioral performance in rats,reduced CGRP and IL-1 β levels,and increased 5-HT content in the brain.Conclusion The Pur@CS-β-CD Gel demonstrates a feasible preparation process,favorable properties for nasal administration,and effective anti-migraine activity,providing an experimental basis for the development of novel nasal delivery systems and migraine therapies.