Study On Preparation Of Nimodipine Nano-Niosome And Evaluation Of Its Brain Targeting

Studies have shown that nonionic surfactant niosome can improve drug’s oral availability and skin permeability.Gardenia jasminoides extract niosome is administered by intragastric administration in rats,drug concentration in brain is increased by 12 times.Whether the niosome carrier can significantly improve chemical drug’s brain targeting,is it due to the additive property or the carrier structure,no related research has been reported so far.In this paper,Nimodipine niosome was first prepared by thin film dispersion method,the formulation and process of preparing Nimodipine niosome were optimized.Drug loading and encapsulation efficiency,scanning electron microscopy（SEM）,transmission electron microscopy（TEM）,particle size and zeta potential were used to investigate the characteristics of Nimodipine niosome.In the PC12 cell experiment and animal experiments,Nimodipine pure drug,a simple mixture of Nimodipine and Span 60 and cholesterol were used as a reference to see if Nimodipine niosome can improve Nimodipine’s brain targeting and nonionic surfactant niosome increasing drug targeting is due to additive properties or carrier shape.The results showed that when the mass ratio of Span-60,cholesterol and Nimodipine was 10:2:1,the ultrasonic power was 300W,and the ultrasonic time was4h（5s on,5s off）,a small amount of sodium lauryl sulfate was added to the drug system,niosome with high stability and cell-like structure can be obtained.Among them,the niosome particle size was 193.8 nm,the PDI was 0.396,the potential was-0.320 m V,the encapsulation efficiency was 81.9%,and the drug loading was 6.4%.In the PC12 cell experiment,the Nimodipine niosome subgroup was less toxic to cells than the simple mixture subgroup when the dose of Nimodipine was 50μmol/L and 100μmol/L.In the animal experiment,Nimodipine pure drug,Nimodipine niosome,and simple mixture were administered to 250 g rats at a drug dose of 5 mg/kg.After 4hours of intragastric administration,the concentration of Nimodipine niosome in the brain was 11.9 ng/g,which was 1.53 times and 1.37 times higher than that of the pure drug and simple mixture of Nimodipine in the brain.The ratio of drug concentration in brain after 4 hours administration to plasma AUC_{0-12 h} was 0.020,0.028 and 0.022,respectively.After tail vein injection,the Cmax of the niosome group in plasma was1539.53±329.54 ng/ml,which was 4.89 times and 2.95 times higher than that of the pure drug group and the simple mixture group,respectively.The AUC_{0-4 h}of the niosome group in plasma was 1437.96 ng·h/ml,which was 2.47 times and 1.91 times higher than that of the AUC_0-4h in the pure drug group and the simple mixture group,respectively;the niosome group’s AUC_{0-4 h} in the rat brain tissue was increased by 1.04and 0.67 times,respectively,compared with the AUC_{0-4 h} of pure drug group and simple mixture group in the rat brain tissue.The above results fully demonstrate the non-ionic surfactant niosome’s effects are due to their specific structure and composition.Non-ionic surfactant niosome can effectively promote the delivery of Nimodipine to the brain and improve the brain targeting of Nimodipine,so that Nimodipine can exert better effects.