Preparation And Characterization Of Curcumin-coated Mesoporous Silica Nanoparticles

MSN has gradually become an excellent nanomaterial for clinical treatment and diagnosis.The preparation process and method have gradually matured.Since the 1990 s,nanocarrier materials have been commercialized and industrialized as carriers of new drug delivery systems,and the US FDA and Nano-agents such as paclitaxel and DOX for clinical applications have been approved and produced in other countries.The application of silica in the chemical industry and cosmetics and food additives indicates its excellent compatibility and high safety,Therefore,MSN is expected to become an emerging multifunctional drug carrier and be used in clinical practice.Based on this,this paper uses MSN to entrap the poorly soluble active ingredient curcumin,and evaluates its in vitro and in vivo performance.The main contents are as follows:(1)The CUR in vitro analytical method was established,and the preparation,characterization and in vitro performance evaluation of CUR-MSN@Lip were carried out.The results show that the linear relationship between CUR concentration and peak area is good within a certain concentration range,and the intra-day precision of the method was good,and the methodology met the requirements.CUR-MSN@Lip was prepared by nanoprecipitation combined with film dispersion method.The particle size potential,encapsulation efficiency and drug loading were measured and investigated.The results of transmission electron microscopy showed that the prepared nanocarriers were spherical or elliptical.The phospholipid encapsulated has a distinct shell-core structure.The in vitro release results showed that the release of CUR-MSN and CUR-MSN@Lip was rapid,and the cumulative release rate at 12 hours was 76.5% and 91.8%,respectively,while the cumulative release rate of CUR was only about 25%.The release rate of CUR-MSN@Lip is faster than that of CUR-MSN,which has a significant compatibilizing effect and provides a theoretical basis for the investigation of the in vivo properties.(2)Studies on the uptake of MSN and MSN@Lip by Caco-2 cells showed that MSN and MSN@Lip have excellent safety performance,and there is no obvious cytotoxicity even at high doses.Both MSN and MSN@Lip can be taken up into the cytoplasm by cells,and MSN@Lip increases the uptake of the formulation by Caco-2 cells compared to MSN.In addition to active transport and endocytosis,the uptake of MSN and MSN@Lip may be related to specific cellular receptors.(3)The analytical method of CUR in blank intestinal perfusate was established.The linearity,precision and recovery of the method were in accordance with the requirements of the method.The stability of CUR in the perfusate was good for a certain period of time and the perfusion device did not adsorb to the drug destruction.In the one-way intestinal perfusion experiment in rats,there was a statistical difference in the absorption between CUR and CUR-MSN,indicating that MSN entrapment increased the intestinal absorption rate of CUR.The absorption of CUR-MSN was also statistically different compared to CUR-MSN@Lip,which may be related to the enhancement of MSN intestinal epithelial cell uptake after phospholipid treatment.In vivo imaging results showed that DIR-MSN@Lip enhanced the retention time of the preparation in the gastrointestinal tract,and MSN was mainly concentrated in the stomach,small intestine and liver,and other organs accumulated less.(4)The UPLC/MS-MS analysis method of CUR in rat blood and tissue fluid was established,and the intra-and inter-day precision of the method was studied.The extraction recovery rate of the method was investigated.The results show that the intra-day and inter-day precision is good,and the extraction recovery rate meets the requirements.The in vivo pharmacokinetics of CUR medicinal water suspension,CUR-MSN group and CUR-MSN@Lip group were investigated.The results showed that the relative bioavailability of the CUR-MSN group was 507.8% compared with the CUR drug substance suspension,and the relative bioavailability of the CUR-MSN@Lip group was 907.3%,compared with the CUR-MSN,CUR-The relative bioavailability of the MSN@Lip group was 178.7%.The in vivo absorption of CUR was significantly improved.In the study of tissue distribution,it was found that the drug was mainly distributed in the liver and spleen in the organs,and the distribution in the kidney was more,and it was rarely distributed in the lungs.