Studies On Zedoary Oil Loaded Mesoporous Silica Nanoparticles Based On Supercritical CO₂ Cyclic Impregnation

Zedoary oil is a kind of volatile oils extracted from the dry rhizome of the Traditional Chinese Medicine named zedoary,which has a significant inhibitory effect on malignant tumors.However,Zedoary oil suffers a great limitation in advanced research and application due to its poor water solubility and poor stability.To load volatile oil into nano carriers can improve the solubilization and stability of volatile oil.Mesoporous silica nanoparticles?MSNs?is an excellent drug nanocarrier,which have exhibited great potential on drug research.However,it is still a great challenge to encapsulate drugs,especially volatile oils into the pores of MSNs with satisfied efficacy,stability and safety.The new‘green'technology based on supercritical fluid is an alternative to prepare nanomaterials with a mass of advantages.The zedoary oil loaded mesoporous silica nano-drug delivery system was established for the first time based on supercritical CO₂ cyclic impregnation.Two kinds of nano-drug delivery systems including zedoary oil loaded mesoporous silica nanoparticles?ZO-MSNs,the controlled-release drug delivery?and zedoary oil loaded chitosan grafted MSNs?ZO@CS-MSNs,the target-specific and controlled-release drug delivery?were studied and fabricated in this thesis,which are of great signification to the further research of zedoary oil.The main contents and results are as follows:1.Supercritical CO₂ cyclic impregnation?SCCI?was established for the first time to fabricate ZO-MSNs in this subject,and the drug-loading rate and entrapment rate were evaluated.The results were compared with those from the traditional methods of solution impregnation and supercritical solvent impregnation.It proved that SCCI could overcome the shortages of both control methods and turned to be a potential drug loading strategy with very high drug loads.2.The SCCI had been used to successfully prepared ZO-MSNs.The effects of several key process parameters were investigated,and the results showed that the optimized conditions for ZO-MSNs preparation were atmospheric impregnation time of 0.5h,high pressure impregnation time of 1h under 15Mpa?40?,and cycle-index of 3.The resulted drug load of zedoary oil was 37.5±1.2%and the encapsulation efficacy was 83.2±2.1%.Quantitative analysis by HPLC demonstrated the composition ratio of six primary ingredients in zedoary oil remained constant after the drug loading process.SEM and TEM images and dynamic light scattering measurement showed that ZO-MSNs were uniform spherical particles around 80 nm.The in vitro release experiment showed that zedoary oil in ZO-MSNs had a great slow-release effect in neutral PBS.The results of the thermal stability experiment showed that the stability of zedoary oil was improved clearly after loaded into MSNs.3.The SCCI had been used to successfully prepared ZO@CS-MSNs.The effect of several key process parameters on the drug load were investigated.The results showed that the optimized conditions for ZO@CS-MSNs preparation were pressure of 15 MPa,high pressure impregnation time of 60 min under 40?and cycle-index of 3,and the resulted drug loads of zedoary oil was 41.4±1.2%.Quantitative analysis by high performance liquid chromatography demonstrated the composition ratio of six primary ingredients in zedoary oil remained constant after the drug loading process.SEM and TEM images showed that ZO@CS-MSNs were spheres with diameter about 80 nm and a‘gate'structure was formed by chitosan on the surface of MSNs.Infrared and thermogravimetric analysis were performed to further confirm the structure of ZO@CS-MSNs.In vitro drug release test under different pH conditions indicated that zedoary oil had a well pH-response release behavior.The results of the thermal stability experiment showed that loading zedoary oil into CS-MSNs can improve its thermal stability significantly.