Preparation And Tissue Distribution Of Chitosan Modified Solid Lipid Nanoparticles Loaded With Zedoary Turmeric Oil

Zedoary turmeric oil(ZTO)has a wide range of pharmacological activities,such as pharmacological effects in anti-tumor,anti-virus,anti-thrombosis,etc..However,highly volatile,the poor aqueous solubility,low bioavailability and not suitable for oral administration of ZTO have limited the further development and clinical application.In this study,Chitosan(CS)-modified ZTO loaded with solid lipid nanoparticles(SLN)was prepared and evaluated in vitro and in vivo.HPLC was used to determine the content of germacrone identified as Zedoary oil index components.The results showed that HPLC method is simple,the sensitivity is high,the precision and recovery rate are in line with the requirements,and the specificity and repeatability are good.ZTO was used as a model drug and monostearic acid glyceride as carrier to prepare zedoary oil solid lipid nanoparticles(ZTO-SLN).Then the surface of ZTO-SLN was modified with CS by electrostatic adsorption to prepare chitosan-modified ZTO loaded with solid lipid nanoparticles(CS-ZTO-SLN).Through single factor analysis,the main factors affecting the encapsulation efficiency and particle size of CS-ZTO-SLN were the dosage of lipid material,the proportion of mixed emulsifier and the amount of ZTO.The orthogonal design test was used to optimize the foramulation by using the encapsulation efficiency and particle size of CS-ZTO-SLN as the evaluation index.The optimal prescription of CS-ZTO-SLN is glycerol monostearate 0.15 g,Twain 2 g,glycerol 1.3 g,ZTO 0.4 g,concentration of CS 0.1%,preparation temperature 70?,dropping acceleration 1 mL/min,stirring time 30 min,cooling time 1 h.Preparation of solid lipid nanoparticles preserved in a refrigerator at 4?.The physical and chemical properties of CS-ZTO-SLN including morphology,particle size and distribution,Zeta potential,in vitro release pattern and stability were characterized by laser particle size analyzer,transmission electron microscope and HPLC.The shape of CS-ZTO-SLN prepared by the best prescription was round and sticky.The average particle size of the unmodified SLN was 134.3 nm,the polydispersity coefficient was 0.213,the Zeta potential was-8.93 mV,the average particle size of CS-ZTO-SLN was 210.4 nm,the polydispersity coefficient was 0.335,Zeta potential+9.12 mV.The results showed that CS-ZTO-SLN was successfully prepared through the change of particle size and the reversal of Zeta potential.The pH7.4 PBS solution(20%ethanol)was used as the release medium in vitro.Dynamic dialysis was used to investigate the in vitro drug release characteristics of nanoparticles.The results showed that the drug substance released about 78%at 4 h,ZTO-SLN and CS-ZTO-SLN was approximately 45%and 28%,respectively.The in vitro release curves of ZTO-SLN and CS-ZTO-SLN were fitted to Weibull equations after fitting.And the curves showed burst release and sustained release.The in vitro release results showed that both ZTO-SLN and CS-ZTO-SLN had a sustained release effect compared to the bulk drug.Compared with the ZTO-SLN without CS modification,the sustained release performance was better,probably due to impediment of CS package to drug release.Preliminary stability results showed that the prepared CS-ZTO-SLN has low stability and is recommended to be stored in a low temperature environment.A HPLC method was established to determine the contents of geraniol in mouse tissues.Validated by methodology,this method is accurate and reliable,with specific properties.The drug concentrations in heart,liver,spleen,lung,and kidney tissues at various time points in vivo of ZTO-SLN,CS-ZTO-SLN and ZTO-Inj were investigated.The results showed that the concentration of ZTO-SLN and CS-ZTO-SLN in liver tissue was significantly higher than that in other organizations 0.5 h after administration.SLN targeting was evaluated by targeting parameters and the results showed that CS-ZTO-SLN has strong liver targeting-Using ZTO-Inj as a control,the relative uptake rate of CS-ZTO-SLN in the liver was 5.38,about twice the relative uptake rate of ZTO-SLN.The value of peak concentration of CS-ZTO-SLN in the liver(Ce)was 2.55,that was higher than the Ce value of 1.95 for ZTO-SLN.The targeted efficiency of ZTO-SLN(Te%)increased from 24.50%(ZTO-Inj)to 34.93%,but was lower than 46.24%(CS-ZTO-SLN).The results showed that SLN could change the distribution of ZTO in mice and obtain an ideal liver targeting.And the liver targeting effect of SLN modified with CS was higher than the unmodified ones.