Study On A Novel Huperz-ine A Sustained-release Drug Delivery System Based On Hydrogel Microneedles

Objective:Huperzine A(HupA)is a highly potent,highly selective,reversible acetylcholine inhibitor that is expected to be used in the treatment and memory loss of Alzheimer's disease,inhibiting AchE activity in the brain and increaseing acetylcholine levels.However,HupA has a large side effect on the peripheral cholinergic system,and there are serious adverse reactions such as dizziness,tinnitus,fasciculation,sweating,and abdominal pain.In this study,we selected huperzine A as a model drug to prepare microemulsion containing huperzine A to increase the solubility of Huperzine A,and reduce the toxicity of Huperzine A.The existing dosage forms of HupA are tablets,capsules,injections,etc.,but these dosage forms are not friendly to patients for taking Alzheimer's disease.In order to improve patient compliance,the microemulsion containing HupA is contained in the microneedle,a sustained release preparation which is transdermally administered by a microneedle.This topic is a hydrogel microneedle prepared by esterification of 20%polymethyl vinyl ether with maleic acid and polyethylene glycol 10000,and the effect of PVA/sucrose soluble micro-targeting on transdermal absorption of drugs,and the formation of loaded HupA microemulsion in the microneedle.Methods:The HupA-loaded microemulsion was first prepared and then characterized and evaluated.A method for determining the in vitro content of HupA was established.The pseudo-ternary phase diagram was used as an indicator to select the optimal ratio of microemulsion prescription.The HupA microemulsion was characterized by appearance morphology,particle size,zeta point and polydispersity coefficient.DiO/DiI are a pair of fluorescent pairs.The DiO/DiI microemulsion is diluted with water or ethanol,and then to measure fluorescence intensity of the microemulsions.The FRET effect is used to judge whether the microemulsion is a complete nanoemulsion.The HupA emulsion was loading on 20%polymethyl vinyl ether co-maleic acid or PVA microneedles to construct a novel HupA microemulsion microneedle transdermal drug delivery system.The results of H&E staining showed The prepared microneedles can effectively pass through the skin of rats,and the results of in vivo imaging experiments showed that the drugs contained in the microneedles can be effectively delivered into the skin.PVA microneedle solubility test results showed that the microneedles can be dissolved in the skin of the rat.The PVA microneedles were dissolved in water or ethanol to measure the fluorescence intensity,and the presence of microemulsion in the FRET effect was judgedTo establish a method for determining the content of HupA in rat in vivo dialysate,and to study the local pharmacokinetic characteristics of transdermal delivery of Hup A-loaded microemulsion by micro-dialysis technique,and establish HupA in large The method for determining the content of plasma in rats is to study the pharmacokinetics.Rusults:The results of H&E staining showed that the prepared microneedles could effectively penetrate the rat skin;the microneedle solubility test showed that the microneedles could be dissolved in the rat skin;the results of small animal activity imaging showed that they were contained in The drug in the microneedle can be effectively delivered into the skin.PVA microneedle has FRET effect in aqueous solution while no FRET effect in ethanol.In vitro transdermal results,the in vitro cumulative transdermal amount of PVA microneedles was 163.09 ±32.62?g/ml,the polymethyl vinylated maleic acid microneedle microneedles were 81.21 ±13.53?g/ml,and the passive diffusion was 18.83±6.53?g/ml.In the body microdialysis experiment,the Tmax of the PVA microneedles was 4h min,the Tmax of the polymethylvinylated maleic acid microneedles was 6 h,and the AUC 0-t of the PVA microneedles was 85.91 h-ng/L,polymethyl The vinyl co-maleic acid microneedle AUC0-twas 75.05 h·ng/L;the Cmax of the PVA microneedle was 15.25 ng/mL,and the Cmax of the polymethylvinyl maleic acid microneedle was 15.02 ng/mL.The results showed that the T1/2 of the PVA microneedle was 22.19h,the T1/2 of the polymethylvinyl maleic acid microneedle was 15.06h,and the AUC0-t of the PVA microneedle was 2209.22h·ng/mL.The AUC 0-t of the polymethylvinyl maleic acid microneedles was 1998.43h·ng/mL.Conclusion:HupA microemulsion microneedle transdermal drug delivery system constructed in this subject,the microemulsion is present in the microneedle system with complete formation,and after microneedle transdermal administration,the microemulsion is released from the microneedle into the skin.In order to achieve the purpose of sustained release administration.