Studies On The Design, Synthesis, Characterization Of The Mesoporous Silica/Calcium Salts Composites And The Potential Application In Controlled Drug Release

Anti-tumor drug delivery systems can be selectively concentrated in the pathological site throughsustained release formulations release the drug, and thus achieve the purpose of treatment. Compared totraditional chemical drug therapy, radiation therapy and surgical therapy, DDS has a high efficacy, lessdosing frequency and low toxic side effects, etc. DDS generally includes three parts: drugs, carriers, andtargeting agents. Depending on the action mechanism of targeting agents, targeting agents divided intoactive targeting and passive targeting. Active targeting through the using of specific antibody to the antigenreceptor and the ligand binding interaction, guide carrier transport orientation, controlled release,to exertits anti-tumor activity, including antibodies, immunoconjugates and transferrin protein. Passive targeting isachieved by reducing and non-target site of action organs using specific biological environment of thelesion induced by controlled release of the drug, and thus exert its anti-tumor activity, typically using hightemperature surrounding the tumor cells, acidity, etc.Compared with the macromolecular carrier systems, the magnetic carrier and multi-targeting system，these SiO2-based drug delivery systems nanospheres have many merit，such as bio-toxic, simple synthesisand easy surface modification. Applications in biological materials have been extensively studied.In this thesis, several aspects were studied：(1) We ultilize surface-modified spherical silica dioxide nanospheres as the substrate which has amesoporous structure composite with hydroxyapatite compound (HAP), chondroitin sulfate, calciumcarbonate to synthesize three different inorganic complexes. The material composition and structurecharacterization were studied by using several measurements to tested their morphology, structure andproperties. The results show that the morphology of the three substances unity, uniform particle sizedistribution, contains a lot of pore structure, negative surface charges, which provide good conditions forfuture load drug molecules.(2) With doxorubicin hydrochloride (DOX HCl) as a model of anticancer drugs, we conducted drugload-release experiments with the three inorganic complexes, the use of UV-visible spectrometer to detectthe amount of drug loaded and released. The results showed that DOX can be a lot of loaded on the three materials, comes to93.72%,82.64%and74.34%, respectively, the load rate is higher than the previous results. Release experiments showed thatthe three materials have good pH sensitivity: DOX in acidic conditions can be sustained released from thematerials, in a neutral environment no DOX was released. These results suggest that these three materialsshows controlled release properties and have a good prospect in the drug delivery systems.(3) HepG2cells and Chinese hamster lung cells (V79-4) were used as the cancer cells and normaltissue cell model to study the antitumor activity of the three materials. Experimental results show that theantitumor activity of the three materials to the drug was higher than the pure DOX, improved targeting wasalso found, the activity of CS added material is particularly evident. Lower cell reproduction inhibition rateto normal tissue indicating that the material can be applied to specific cancer cells, this way to achievepassive targeting purposes; after adding a targeting agent (CS), the active targeting effect is obvious. Theresults for further experimental and clinical studies in vivo application have laid a good foundation.Experimental results show that inorganic complexes based on the silica dioxide nanospheres withmesoporous structure can achieve its purpose of targeting through its own PH sensitivity and the ligandinductive effective. The role of guide transport drugs, enhance the anti-tumor activity, inhibit thepropagation of cancer cells was achieved as well. The experimental material synthesized as a carrier hasbroad application prospects in drug delivery and cancer treatment, and future research provides importantexperimental and theoretical basis to further research.