| Hollow mesoporous silica（HMS）is a kind of hollow nano material with mesoporous silica as the shell.The hollow cavity inside can be used to store drugs,and the mesoporous channel on the shell can adjust the release rate of drugs to achieve slow,controlled or rapid release,so it is widely used in the construction of drug delivery system.In this paper,two different types of HMS carriers were prepared.Fenofibrate was used as model drug to study the influence of carrier preparation process on carrier structure,the relationship between drug loading method and drug release performance,and the release mechanism of corresponding drug loading system.The self template method was used to prepare Si O2 microspheres as hollow template and surfactant cetyltrimethylammonium bromide（CTAB）as the shell mesoporous template.Using ammonia as catalyst and tetraethyl orthosilicate（TEOS）as silicon source,The hollow mesoporous silica nanospheres（HMSNs）were prepared by the proper method for separation and calcination of surfactants.Then,On this basis,the organic reagent 1,2-di（triethoxysilyl）ethane was added to bridge the organic groups onto the silicon skeleton,and then hollow periodic mesporous organosilicas（HPMO）with hydrophobic organic alkyl group was obtained.The effects of TEOS content,etching time and temperature,CTAB removal method,calcination time and temperature on the preparation of carrier were studied.The preparation process of HMSNs and HPMO was optimized.The model drug fenofibrate was loaded on HMSNs and HPMO,and the drug loading results were compared by changing the drug load concentration,drug load method and drug load solvent.The results showed that the drug load was in direct proportion to the drug concentration;the drug load of coprecipitation method was higher than that of solvent adsorption method;the drug load of ethyl acetate solution was higher than that of acetone and ethanol solution;the drug load of HPMO was higher than that of HMSNs,and the drug load was 35.39%and 30.22%,respectively when the drug concentration was 100 mg/m L.Fourier transform infrared spectroscopy（FTIR）,scanning electron microscope（SEM）,high-resolution transmission electron microscope（HRTEM）,X-ray diffraction（XRD）,nitrogen adsorption-desorption test were used to analyze the morphology,skeleton structure,specific surface area,pore volume,pore diameter and drug load of the two carrier materials before and after drug load.The results showed that the two kinds of carrier materials had good order,regular particle size and good dispersibility.The average particle size,pore volume and specific surface area of HMSNs and HPMO were 3.87 nm 0.89 cm~3/g 819.33 m~2/g and 4.95nm 1.11 cm~3/g 896.75 m~2/g,respectively.The larger particle size,pore volume and specific surface area of HPMO than HMSNs were the reasons for the larger drug load.The conditions of drug concentration,rotation speed,SDS dosage,drug loading method and solvent were screened to get the best in vitro dissolution conditions.An in vitro analysis method of aqueous solution and four kind of p H dissolution media were established to conduct in vitro dissolution tests and analyze the drug dissolution behavior.The results showed that in the five dissolution media,the drug load on HMSNs increased the dissolution rate of the drug in vitro to a certain extent,while the HPMO prepared had different degree of sustained-release effect due to its shell structure of siloxane and enhanced hydrophobicity.The release of the two drug delivery systems was in accordance with the ritger peppas release model,the drug release accords with Fick,s diffusion law,and the release mechanism is irregular release. |
