Effect of loading and release factors in vitro of mesoporous silica nanoparticles as drug carriers for nifedipine
Tutor / director / evaluatorManero Planella, José María
Document typeMaster thesis
Rights accessOpen Access
This project is a part of the development of biomaterials for bone tissue engineering for type 2 diabetic patients. The latters show a higher rejection implant rate than healthy people. When people are affected by type 2 diabetes they develop insulin resistance and the glucose accumulates in blood. Hyperglycemia leads to the ROS (reactive oxygen species) production. The ROS takes part of an equilibrium (redox biology). They are used by cells in several mechanisms such as signal transduction, cellular proliferation or differentiation and development. However if they are overproduced, they become cytotoxic and leads to oxidative stress. ROS have an impact on bone remodeling and enhance the resorption of bones. In the case of implant, a local treatment of ROS is needed to help the bone to form around the implant. To counterbalance the oxidative stress from the ROS, the nifedipine will be used for its anti-oxidative properties. But this drug is light sensitive and poorly soluble in water and it affects its bioavailability. To protect it and have a local treatment, silica mesoporous nanoparticles are used. Thanks to their high surface area and their high pore volume, it is possible to load a large quantity of drug inside the pores via adsorption. And the nanoparticles can bring a protection to the drug. The aims of the project is to chose the best way to load nanoparticles among different methods and to choose a release method between three ones. The first step of this project has been the synthesis of nanoparticles. The technique used is a sol-gel process where silica is obtained by the hydrolysis of TEOS on CTAB in a basic medium. A co-condensation was driven with APTES, the functionalization. The second step was the loading of the nanoparticles with nifedipine. Four methods have been studied. The characterization has been done by Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA). The FTIR gives evidence of the presence of nifedipine and the TGA allows to quantify it. The results show different percentage of loading which depend on the method used. The third step was to study the release of nifedipine. Three different methods have been used: dialysis, USP apparatus and tubes. The characterization of the release has been processed by UV-vis NIR spectrophotometry at 238 nm. The three methods show a release of the drug but one is preferred.